## Protocol Section
### Identification Module
**NCT ID:** NCT02838979

**Brief Title:** Trial of Oral Glutamine on Mitochondrial Function in CKD

**Official Title:** Randomized Cross-over Trial of Oral L-Glutamine vs Maltodextrin on Mitochondrial Function in Chronic Kidney Disease

#### Organization Study ID Info
**ID:** 47861
#### Organization
**Class:** OTHER
**Full Name:** University of Washington
#### Secondary ID Infos
**ID:** 5K23DK099442
**Link:** https://reporter.nih.gov/quickSearch/5K23DK099442
**Type:** NIH
### Status Module
#### Completion Date
**Date:** 2018-01-31

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-07-14

**Type:** ACTUAL

**Last Update Submit Date:** 2022-06-21

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2017-10-01

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2022-07-14

**Type:** ACTUAL

**Results First Submit Date:** 2021-12-03

**Results First Submit QC Date:** 2022-06-21

#### Start Date
**Date:** 2016-02-25

**Type:** ACTUAL

**Status Verified Date:** 2022-03

#### Study First Post Date
**Date:** 2016-07-20
**Type:** ESTIMATED
**Study First Submit Date:** 2016-07-08
**Study First Submit QC Date:** 2016-07-15
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** New York Medical College

**Class:** OTHER

**Name:** Emory University

**Class:** OTHER

**Name:** Vanderbilt University

**Class:** NIH

**Name:** National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Washington

#### Responsible Party

**Investigator Affiliation:** University of Washington

**Investigator Full Name:** Jonathan Himmelfarb

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The primary goal of proposed investigation is to study the impact of oral glutamine supplementation on muscle mitochondrial and endothelial cell function measured mitochondrial energetics and vascular function using 31P magnetic resonance spectroscopy and optical spectroscopy (MRS/OS) among persons with moderate-severe CKD. The secondary objective is to describe the impact of oral glutamine supplementation on mitochondrial metabolic profile as well as inflammatory and oxidative stress biomarkers among persons with chronic kidney disease.

**Detailed Description:** Chronic kidney disease is associated with endothelial cell dysfunction and muscle wasting contributing to the heightened risk of cardiovascular morbidity, mortality and functional limitation. Accumulation of toxins in renal disease may adversely impact endothelial cell nitric oxide bioavailability and endothelial Nitric Oxide Synthase (eNOS) function consequently heightening oxidative stress and suppressing mitochondrial biogenesis. To date no studies have investigated potential therapies for endothelial and muscle dysfunction in renal disease target mitochondrial metabolic and energetic processes.

Animal studies of uremia underscore mitochondrial dysfunction as a potential precursor for endothelial dysfunction. In particular, uremia has been linked to a proteomic signature indicative of metabolic blockage of TCA cycle activity and fatty acid beta-oxidation. Both of these processes are localized to the mitochondria and may suggest that decreased mitochondrial mass or function may augur endothelial dysfunction in renal disease.

Glutamine, an anaplerotic agent and precursor to the antioxidant glutathione, is a potential therapeutic agent bypassing the metabolic block associated with reduced TCA cycle and improving antioxidant reserve. The primary goal of proposed investigation is to study the impact of oral glutamine supplementation on muscle mitochondrial and endothelial cell function measured mitochondrial energetics and vascular function using 31P MRS/OS among persons with moderate-severe CKD. The secondary objective is to describe the impact of oral glutamine supplementation on mitochondrial metabolic profile as well as inflammatory and oxidative stress biomarkers among persons with chronic kidney disease.

### Conditions Module

**Conditions:**

- Cardiovascular Disease

- Sarcopenia

- Endothelial Dysfunction

- Muscle Mitochondrial Function

- Kidney Disease

**Keywords:**

- Glutamine

- Chronic Kidney Disease

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** TRIPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 11

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Subjects will receive 0.4 g/kg/day of L-glutamine (Nutrestore, EMMAUS Life Sciences, Inc Torrance, CA) in three divided daily doses OR identical appearing maltodextrin powder.

Duration 2 weeks

**Intervention Names:**

- Dietary Supplement: First Intervention (14 days)

- Other: Washout (3 weeks)

- Dietary Supplement: Second Intervention (14 days)

**Label:** Oral L-Glutamine first, then Maltodextrin

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Subjects will crossover to receiving the study product which they did not receive in the first period.

Either 0.4 g/kg/day of L-glutamine in three divided daily doses OR identical appearing maltodextrin powder.

Duration 2 weeks

**Intervention Names:**

- Dietary Supplement: First Intervention (14 days)

- Other: Washout (3 weeks)

- Dietary Supplement: Second Intervention (14 days)

**Label:** Maltodextrin first, then L-glutamine

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Maltodextrin first, then L-glutamine

- Oral L-Glutamine first, then Maltodextrin

**Description:** Oral Glutamine or Maltodextrin for 2 weeks

**Name:** First Intervention (14 days)

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- Maltodextrin first, then L-glutamine

- Oral L-Glutamine first, then Maltodextrin

**Description:** No study product is taken prior to beginning crossover

**Name:** Washout (3 weeks)

**Type:** OTHER

#### Intervention 3

**Arm Group Labels:**

- Maltodextrin first, then L-glutamine

- Oral L-Glutamine first, then Maltodextrin

**Description:** Oral Glutamine or Maltodextrin for 2 weeks

**Name:** Second Intervention (14 days)

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Other Outcomes

**Description:** To test if glutamine improves plasma NAD+ compared to placebo. Plasma NAD+ concentrations were quantified in mM using 31p MRS based in vivo assay.

**Measure:** Plasma NAD+ Levels

**Time Frame:** 2 weeks

#### Primary Outcomes

**Description:** 31P MRS/OS was used to measure mitochondrial phosphorylation capacity (ATPmax).

**Measure:** Muscle Mitochondrial Function

**Time Frame:** 2 weeks

#### Secondary Outcomes

**Description:** To test if glutamine improves objective isometric muscle fatigue by comparing the measurement of FTI from each arm. Muscle fatigability was tested by calculating FTI as the area under the force-time curve during isometric force generated at 70 % of maximal voluntary contraction (MVC),

**Measure:** Change in Force-time Integral Area Under the Curve in Active Agent vs. Placebo

**Time Frame:** 2 weeks

**Description:** To test the effect of glutamine supplementation on muscle endurance, sum of the muscle force (force-time integral, FTI, N\*s) normalized to maximum voluntary contraction (MVC, N) generated during voluntary contraction.

**Measure:** Muscle Fatigue

**Time Frame:** 2 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Adults between 20 and 69 years of age
* Diagnosis of moderate-severe CKD, defined in this study as an estimated glomerular filtration rate (eGFR) of ≤60ml/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration equation
* Ability to understand and provide informed consent to participate in the study

Exclusion Criteria:

* On chronic dialysis
* Expectation to start dialysis within 6 months or dialysis access in place.
* Pregnant
* Have physical immobility (defined by wheelchair use)
* Insulin dependent diabetes
* Have implants incompatible with MRI
* Exercise limiting cardiopulmonary disease (e.g. angina, severe heart valve disease, severe COPD, coronary ischemia)
* Use of anticoagulation (i.e. warfarin)
* Baseline systolic blood pressure \>160 or diastolic blood pressure \>100
* Inflammatory conditions (e.g. autoimmune disease, HIV)
* Thyroid disease
* Dementia or inability to consent
* Cirrhosis, active/chronic hepatitis
* Use medications interfering with muscle or mitochondrial function, including steroids, anti-psychotic, Coenzyme Q-10, immunosuppresssives, antivirals, and muscle relaxants
* Weight \>300 lbs
* Personal history or family history of deep vein thrombosis, pulmonary embolism
* Active malignancy
* Patients hospitalized within the past 60 days for any reason.
* Patients with a history of a major atherosclerotic event (defined as combined incidence of myocardial infarction, urgent target-vessel revascularization, coronary bypass surgery, and stroke) within 3 months

**Maximum Age:** 69 Years

**Minimum Age:** 20 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Seattle

**Country:** United States

**Facility:** Kidney Research Institute, University of Washington

**State:** Washington

**Zip:** 98104

#### Overall Officials

**Official 1:**

**Affiliation:** Kidney Research Insitute

**Name:** Jonathan Himmelfarb, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** Ziegler TR, Benfell K, Smith RJ, Young LS, Brown E, Ferrari-Baliviera E, Lowe DK, Wilmore DW. Safety and metabolic effects of L-glutamine administration in humans. JPEN J Parenter Enteral Nutr. 1990 Jul-Aug;14(4 Suppl):137S-146S. doi: 10.1177/0148607190014004201.

**PMID:** 2119459

**Citation:** Amara CE, Marcinek DJ, Shankland EG, Schenkman KA, Arakaki LS, Conley KE. Mitochondrial function in vivo: spectroscopy provides window on cellular energetics. Methods. 2008 Dec;46(4):312-8. doi: 10.1016/j.ymeth.2008.10.001. Epub 2008 Oct 16.

**PMID:** 18930151

**Citation:** Jones DP, Liang Y. Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med. 2009 Nov 15;47(10):1329-38. doi: 10.1016/j.freeradbiomed.2009.08.021. Epub 2009 Aug 26.

**PMID:** 19715755

## Document Section

### Large Document Module

#### Large Docs

- Date: 2015-12-07

- Filename: Prot_SAP_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: True

- Label: Study Protocol and Statistical Analysis Plan

- Size: 516448

- Type Abbrev: Prot_SAP

- Upload Date: 2021-12-02T18:44

- Date: 2016-03-24

- Filename: ICF_001.pdf

- Has ICF: True

- Has Protocol: False

- Has SAP: False

- Label: Informed Consent Form

- Size: 1796522

- Type Abbrev: ICF

- Upload Date: 2021-12-02T18:45

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

- ID: D000009133

- Term: Muscular Atrophy

- ID: D000020879

- Term: Neuromuscular Manifestations

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000001284

- Term: Atrophy

- ID: D000020763

- Term: Pathological Conditions, Anatomical

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10698

- Name: Kidney Diseases

- Relevance: HIGH

- As Found: Kidney Disease

- ID: M28396

- Name: Sarcopenia

- Relevance: HIGH

- As Found: Sarcopenia

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12090

- Name: Muscular Atrophy

- Relevance: LOW

- As Found: Unknown

- ID: M4589

- Name: Atrophy

- Relevance: LOW

- As Found: Unknown

- ID: M22619

- Name: Neuromuscular Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M22519

- Name: Pathological Conditions, Anatomical

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T4202

- Name: Oculocerebral Syndrome With Hypopigmentation

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000055948

- Term: Sarcopenia

- ID: D000007674

- Term: Kidney Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

### Intervention Browse Module - Browse Branches

- Abbrev: AA

- Name: Amino Acids

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: T6

- Name: Glutamine

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** L-Glutamine

**Deaths Num At Risk:** 11

**Description:** L-glutamine: Oral Glutamine for 2 weeks at dose of 0.4mg/kg/day in three divided daily doses

**ID:** EG000

**Other Num at Risk:** 11

**Serious Number At Risk:** 11

**Title:** L-Glutamine

**Group ID:** EG001

**Title:** Maltodextrin

**Deaths Num At Risk:** 11

**Description:** Identical appearing maltodextrin powder.

**ID:** EG001

**Other Num at Risk:** 11

**Serious Number At Risk:** 11

**Title:** Maltodextrin

**Frequency Threshold:** 0

**Time Frame:** 7 weeks

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 6

**Group ID:** BG001

**Value:** 5

**Group ID:** BG002

**Value:** 11

**Units:** Participants

### Group

**ID:** BG000

**Title:** L-Glutamine First, Then Maltodextrin

**Description:** Subjects will first receive 0.4 g/kg/day of L-glutamine (Nutrestore, EMMAUS Life Sciences, Inc Torrance, CA) first, then crossover taking Maltodextrin.

### Group

**ID:** BG001

**Title:** Maltodextrin First, Then L-glutamine

**Description:** Subjects will first receive Identical appearing maltodextrin powder first, then crossover to taking L-glutamine.

### Group

**ID:** BG002

**Title:** Total

**Description:** Total of all reporting groups

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 16.6

**Value:** 57

#### Measurement

**Group ID:** BG001

**Spread:** 9.8

**Value:** 58

#### Measurement

**Group ID:** BG002

**Spread:** 13.3

**Value:** 58

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 4

#### Measurement

**Group ID:** BG001

**Value:** 1

#### Measurement

**Group ID:** BG002

**Value:** 5

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 2

#### Measurement

**Group ID:** BG001

**Value:** 4

#### Measurement

**Group ID:** BG002

**Value:** 6

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**Category Title:** Hispanic or Latino

#### Measurement

**Group ID:** BG000

**Value:** 6

#### Measurement

**Group ID:** BG001

**Value:** 5

#### Measurement

**Group ID:** BG002

**Value:** 11

**Category Title:** Not Hispanic or Latino

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**Category Title:** American Indian or Alaska Native

#### Measurement

**Group ID:** BG000

**Value:** 1

#### Measurement

**Group ID:** BG001

**Value:** 2

#### Measurement

**Group ID:** BG002

**Value:** 3

**Category Title:** Asian

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**Category Title:** Native Hawaiian or Other Pacific Islander

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**Category Title:** Black or African American

#### Measurement

**Group ID:** BG000

**Value:** 5

#### Measurement

**Group ID:** BG001

**Value:** 3

#### Measurement

**Group ID:** BG002

**Value:** 8

**Category Title:** White

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**Category Title:** More than one race

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 6

#### Measurement

**Group ID:** BG001

**Value:** 5

#### Measurement

**Group ID:** BG002

**Value:** 11

**Class Title:** United States

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age, Continuous
**Unit of Measure:** years
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Ethnicity (NIH/OMB)
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Race (NIH/OMB)
**Unit of Measure:** Participants
### Measure 5
**Parameter Type:** NUMBER
**Title:** Region of Enrollment
**Unit of Measure:** participants
## Results Section - More Information Module
### Certain Agreement
### Point of Contact
**Email:** ayerse@uw.edu
**Organization:** University of Washington
**Phone:** 206-685-1423
**Title:** Ernest Ayers
## Results Section - Outcome Measures Module
### Outcome Measure 1
#### Analysis
**CI Lower Limit:** 
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 
**CI Upper Limit:** 
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_DEVIATION
**Dispersion Value:** 0.34
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY
**Other Analysis Description:** 
**P-Value:** 0.15
**P-Value Comment:** P-value for the interaction of treatment and sequence
**Parameter Type:** Mean Difference (Final Values)
**Parameter Value:** -0.01
**Statistical Comment:** Two-way ANOVA was used to assess differences between the groups
**Statistical Method:** ANOVA
**Tested Non-Inferiority:** 
### Outcome Measure 2
#### Analysis
**CI Lower Limit:** 
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 
**CI Upper Limit:** 
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_DEVIATION
**Dispersion Value:** 22.18
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY
**Other Analysis Description:** 
**P-Value:** 0.86
**P-Value Comment:** P-value for the interaction of treatment and sequence
**Parameter Type:** Mean Difference (Final Values)
**Parameter Value:** -7.39
**Statistical Comment:** Two-way ANOVA was used to assess differences between the groups
**Statistical Method:** ANOVA
**Tested Non-Inferiority:** 
### Outcome Measure 3
#### Analysis
**CI Lower Limit:** 
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 
**CI Upper Limit:** 
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_DEVIATION
**Dispersion Value:** 1.04
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY
**Other Analysis Description:** 
**P-Value:** 0.44
**P-Value Comment:** P-value for the interaction of treatment and sequence
**Parameter Type:** Median Difference (Final Values)
**Parameter Value:** -0.10
**Statistical Comment:** Two-way ANOVA was used to assess differences between the groups
**Statistical Method:** ANOVA
**Tested Non-Inferiority:** 
### Outcome Measure 4
#### Analysis
**CI Lower Limit:** 
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 
**CI Upper Limit:** 
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_DEVIATION
**Dispersion Value:** 0.21
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY
**Other Analysis Description:** 
**P-Value:** 0.36
**P-Value Comment:** P-value for the interaction of treatment and sequence
**Parameter Type:** Mean Difference (Final Values)
**Parameter Value:** 0.06
**Statistical Comment:** Two-way ANOVA was used to assess differences between the groups
**Statistical Method:** ANOVA
**Tested Non-Inferiority:** 
### Outcome Measure 5
#### Analysis
**CI Lower Limit:** 
**CI Number of Sides:** TWO_SIDED
**CI Percentage Value:** 
**CI Upper Limit:** 
**CI Upper Limit Comment:** 
**Dispersion Type:** STANDARD_DEVIATION
**Dispersion Value:** 7.87
**Estimate Comment:** 
**Group Description:** 
**Non-Inferiority Comment:** 
**Non-Inferiority Type:** SUPERIORITY
**Other Analysis Description:** 
**P-Value:** 0.60
**P-Value Comment:** P-value for the interaction of treatment and sequence
**Parameter Type:** Mean Difference (Final Values)
**Parameter Value:** -0.45
**Statistical Comment:** Two-way ANOVA was used to assess differences between the groups
**Statistical Method:** ANOVA
**Tested Non-Inferiority:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.30
- **Upper Limit:** 
- **Value:** 0.88
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.34
- **Upper Limit:** 
- **Value:** 0.90
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 24.07
- **Upper Limit:** 
- **Value:** 58.87
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 21.22
- **Upper Limit:** 
- **Value:** 52.36
**Title:** 
#### Outcome Measure 3
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 1.09
- **Upper Limit:** 
- **Value:** 2.52
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 1.03
- **Upper Limit:** 
- **Value:** 2.41
**Title:** 
#### Outcome Measure 4
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.25
- **Upper Limit:** 
- **Value:** 0.95
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.19
- **Upper Limit:** 
- **Value:** 0.98
**Title:** 
#### Outcome Measure 5
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 6.834
- **Upper Limit:** 
- **Value:** 23.6
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 8.967
- **Upper Limit:** 
- **Value:** 23.22
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** 31P MRS/OS was used to measure mitochondrial phosphorylation capacity (ATPmax).
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 2 weeks
**Title:** Muscle Mitochondrial Function
**Type:** PRIMARY
**Unit of Measure:** mM ATP/s
##### Group
**Description:** L-glutamine: Oral Glutamine for 2 weeks at dose of 0.4mg/kg/day in three divided daily doses
**ID:** OG000
**Title:** L-Glutamine
##### Group
**Description:** Identical appearing maltodextrin powder.

Maltodextrin: Oral maltodextrin as described for the active agent: 2 weeks at dose of 0.4mg/kg/day in three divided daily doses.
**ID:** OG001
**Title:** Maltodextrin
#### Outcome Measure 2
**Description:** To test if glutamine improves objective isometric muscle fatigue by comparing the measurement of FTI from each arm. Muscle fatigability was tested by calculating FTI as the area under the force-time curve during isometric force generated at 70 % of maximal voluntary contraction (MVC),
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 2 weeks
**Title:** Change in Force-time Integral Area Under the Curve in Active Agent vs. Placebo
**Type:** SECONDARY
**Unit of Measure:** N*s
##### Group
**Description:** L-glutamine: Oral Glutamine for 2 weeks at dose of 0.4mg/kg/day in three divided daily doses
**ID:** OG000
**Title:** L-Glutamine
##### Group
**Description:** Identical appearing maltodextrin powder.

Maltodextrin: Oral maltodextrin as described for the active agent: 2 weeks at dose of 0.4mg/kg/day in three divided daily doses.
**ID:** OG001
**Title:** Maltodextrin
#### Outcome Measure 3
**Description:** To test the effect of glutamine supplementation on muscle endurance, sum of the muscle force (force-time integral, FTI, N\*s) normalized to maximum voluntary contraction (MVC, N) generated during voluntary contraction.
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 2 weeks
**Title:** Muscle Fatigue
**Type:** SECONDARY
**Unit of Measure:** s-1
##### Group
**Description:** L-glutamine: Oral Glutamine for 2 weeks at dose of 0.4mg/kg/day in three divided daily doses
**ID:** OG000
**Title:** L-Glutamine
##### Group
**Description:** Identical appearing maltodextrin powder.

Maltodextrin: Oral maltodextrin as described for the active agent: 2 weeks at dose of 0.4mg/kg/day in three divided daily doses.
**ID:** OG001
**Title:** Maltodextrin
#### Outcome Measure 4
**Description:** To test if glutamine improves plasma NAD+ compared to placebo. Plasma NAD+ concentrations were quantified in mM using 31p MRS based in vivo assay.
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 2 weeks
**Title:** Plasma NAD+ Levels
**Type:** OTHER_PRE_SPECIFIED
**Unit of Measure:** mM
##### Group
**Description:** L-glutamine: Oral Glutamine for 2 weeks at dose of 0.4mg/kg/day in three divided daily doses
**ID:** OG000
**Title:** L-Glutamine
##### Group
**Description:** Identical appearing maltodextrin powder.

Maltodextrin: Oral maltodextrin as described for the active agent: 2 weeks at dose of 0.4mg/kg/day in three divided daily doses.
**ID:** OG001
**Title:** Maltodextrin
#### Outcome Measure 5
**Description:** To test if glutamine improves maximal voluntary contraction compared to placebo. Maximum voluntary contraction (MVC) was determined by the isometric force generated using first dorsal interosseous (FDI) muscle against a force transducer.
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 2 weeks
**Title:** Maximal Voluntary Contraction
**Type:** POST_HOC
**Unit of Measure:** N/m
##### Group
**Description:** L-glutamine: Oral Glutamine for 2 weeks at dose of 0.4mg/kg/day in three divided daily doses
**ID:** OG000
**Title:** L-Glutamine
##### Group
**Description:** Identical appearing maltodextrin powder.

Maltodextrin: Oral maltodextrin as described for the active agent: 2 weeks at dose of 0.4mg/kg/day in three divided daily doses.
**ID:** OG001
**Title:** Maltodextrin
### Participant Flow Module
#### Group
**Description:** Subjects will receive 0.4 g/kg/day of L-glutamine (Nutrestore, EMMAUS Life Sciences, Inc Torrance, CA) in three divided daily doses. Duration 2 weeks

L-glutamine: Oral Glutamine for 2 weeks at dose of 0.4mg/kg/day in three divided daily doses
**ID:** FG000
**Title:** Oral L-Glutamine First, Then Maltodestrin
#### Group
**Description:** Identical appearing maltodextrin powder.

Maltodextrin: Oral maltodextrin as described for the active agent: 2 weeks at dose of 0.4mg/kg/day in three divided daily doses.
**ID:** FG001
**Title:** Maltodextrin First, Then L-glutamine
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 6
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 5
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 6
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 5
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
**Has Results:** True