## Protocol Section
### Identification Module
**NCT ID:** NCT06425042

**Acronym:** RESTORENAD

**Brief Title:** Nicotinamide Riboside Supplementation and Exercise Training to Promote Healthy Longevity

**Official Title:** Boosting the NAD+ Levels in Older Individuals Via Nicotinamide Riboside Supplementation and Exercise Training to Promote Metabolic Health

#### Organization Study ID Info
**ID:** 23-041
#### Organization
**Class:** OTHER
**Full Name:** Finis Terrae University
### Status Module
#### Completion Date
**Date:** 2026-03

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-17

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-03-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-17
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Finis Terrae University

#### Responsible Party

**Investigator Affiliation:** Finis Terrae University

**Investigator Full Name:** Rodrigo Mancilla

**Investigator Title:** Doctor, PhD

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The prevalence of age-related chronic diseases (like obesity, type 2 diabetes and cardiovascular diseases) is mounting worldwide, reaching pandemic proportions. These age-related chronic diseases are associated with diminished skeletal muscle mitochondrial function in humans. Nicotinamide adenosine dinucleotide (NAD) is a coenzyme that regulates mitochondrial function, therefore, plays an important role in energy metabolism. Importantly, it has been shown that high cellular NAD+ levels as well as a high NAD+/NADH ratio promote metabolic and mitochondrial health. In contrast, NAD+ bioavailability declines upon aging in humans as well as in animal models of metabolic disorders and type 2 diabetes. These findings fuel the notion of boosting the NAD+ bioavailability in order to improve metabolic disturbances and mitochondrial dysfunction in aged individuals. Supplementation with nicotinamide riboside (NR), a naturally occurring form of vitamin B3, boosts cellular NAD+ levels. However, in contrast to animal studies, NR supplementation in humans has so far been unsuccessful in improving skeletal muscle mitochondrial function, exercise capacity or insulin sensitivity. Interestingly, Recently, it has been suggested that metabolic conditions where NAD+ levels become limited, is needed for NR supplementation to exert beneficial health effects. This metabolic condition could be achieved by exercise. However, studies combining NR and exercise are lacking, and that is why we will perform the present study.

### Conditions Module

**Conditions:**

- Healthy Aging

- Lifestyle-related Condition

- Metabolic Diseases

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Masking Description:** Double blinded

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 28

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** This arm will ingest NR orally and perform exercise training

**Intervention Names:**

- Dietary Supplement: Nicotinamide Riboside (NR)

**Label:** NR+EXTR

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** This arm will ingest placebo orally and perform exercise training

**Intervention Names:**

- Dietary Supplement: Placebo

**Label:** PLA+EXTR

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- NR+EXTR

**Description:** Participants will ingest 1g/d of NR orally during 12 weeks in parallel to a exercise training program

**Name:** Nicotinamide Riboside (NR)

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- PLA+EXTR

**Description:** Participants will ingest 1g/d of placebo orally during 12 weeks in parallel to a exercise training program

**Name:** Placebo

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Primary Outcomes

**Description:** Skeletal muscle mitochondrial respiratory capacity will be measured in permeabilized fibres.

**Measure:** Skeletal muscle mitochondrial respiratory capacity

**Time Frame:** 12 weeks

**Description:** Proteins content of oxidative phosphorylation system will be quantified from muscle biopsy

**Measure:** Skeletal muscle mitochondrial content

**Time Frame:** 12 weeks

#### Secondary Outcomes

**Description:** Quantification of proteins content of oxidative phosphorylation system in muscle biopsies

**Measure:** Quantification of proteins that regulate oxidative metabolism

**Time Frame:** 12 weeks

**Description:** Maximal aerobic capacity will be measure upon a progressive cycling test

**Measure:** Maximal aerobic capacity

**Time Frame:** 12 weeks

**Description:** Walking speed and distance will be measured via the 6-minutes walking test

**Measure:** Walking speed and distance

**Time Frame:** 12 weeks

**Description:** Time spent on performing seating and standing transitions will be measured upon the timed-up and go test

**Measure:** Seating and standing transitions

**Time Frame:** 12 weeks

**Description:** Exercise efficiency will be measured upon a sub maximal cycling test and indirect calorimetry

**Measure:** Exercise efficiency

**Time Frame:** 12 weeks

**Description:** Intrahepatic liver fat content will be measured by 1H-MRS

**Measure:** Intrahepatic liver fat content

**Time Frame:** 12 weeks

**Description:** body weight will be measured in kilograms

**Measure:** Body weight

**Time Frame:** 12 weeks

**Description:** total muscle mass will be measured in kilograms and/or percentage

**Measure:** Total muscle mass

**Time Frame:** 12 weeks

**Description:** Total fat mass will be measured in kilograms and/or percentage

**Measure:** Total fat mass

**Time Frame:** 12 weeks

**Description:** Fat-free mass will be measured in kilograms and/or percentage

**Measure:** Fat-free mass

**Time Frame:** 12 weeks

**Description:** NAD+ levels in circulation and in skeletal muscle

**Measure:** NAD+ levels

**Time Frame:** 12 weeks

**Description:** 24h Blood pressure will be measured with a continuous blood pressure holder device

**Measure:** 24h Blood pressure

**Time Frame:** 12 weeks

**Description:** Heart rate variability will be measured with a continuos electrocardiogram monitor device

**Measure:** Heart rate variability

**Time Frame:** 12 weeks

**Description:** Resting energy expenditure will be measured by indirect calorimetry

**Measure:** Resting energy expenditure

**Time Frame:** 12 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Participants are able to provide signed and dated written informed consent prior to any study specific procedures
* Aged ≥ 60 and ≤ 80 years
* Body mass index (BMI) 25 - 35 kg/m2
* Stable dietary habits (no weight loss or gain \> 5 kg in the past 3 months)
* No signs of active cardiovascular disease, liver or kidney malfunction

Exclusion Criteria:

* Patients with congestive heart failure and and/or severe renal and or liver insufficiency
* Uncontrolled hypertension
* Any contra-indication for MRI scanning
* Alcohol consumption of \> 3 servings per day for man and \>2 servings per day for woman
* Smoking
* Unstable body weight (weight gain or loss \> 5kg in the last 3 months)
* Engagement in structured exercise activities \> 2 hours a week
* Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator which would possibly hamper our study results
* Use of food supplements containing NR or Resveratrol (similar working mechanisms)

**Healthy Volunteers:** True

**Maximum Age:** 80 Years

**Minimum Age:** 60 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** rmancilla@uft.cl

**Name:** Rodrigo Mancilla, PhD

**Phone:** +56953676588

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Santiago

**Contacts:**

***Contact 1:***

- **Name:** Rodrigo Mancilla, PhD

- **Role:** CONTACT

**Country:** Chile

**Facility:** Finis Terrae University

**State:** Region Metropolitana

**Status:** RECRUITING

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M11639

- Name: Metabolic Diseases

- Relevance: HIGH

- As Found: Metabolic Diseases

### Condition Browse Module - Meshes

- ID: D000008659

- Term: Metabolic Diseases

### Intervention Browse Module - Ancestors

- ID: D000014803

- Term: Vitamin B Complex

- ID: D000014815

- Term: Vitamins

- ID: D000018977

- Term: Micronutrients

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000960

- Term: Hypolipidemic Agents

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000057847

- Term: Lipid Regulating Agents

- ID: D000014665

- Term: Vasodilator Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: VaDiAg

- Name: Vasodilator Agents

- Abbrev: Lipd

- Name: Lipid Regulating Agents

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M12476

- Name: Niacinamide

- Relevance: HIGH

- As Found: Continuing

- ID: M12465

- Name: Niacin

- Relevance: HIGH

- As Found: Continuing

- ID: M12479

- Name: Nicotinic Acids

- Relevance: HIGH

- As Found: Continuing

- ID: M8618

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M17558

- Name: Vitamins

- Relevance: LOW

- As Found: Unknown

- ID: M17546

- Name: Vitamin B Complex

- Relevance: LOW

- As Found: Unknown

- ID: M21009

- Name: Micronutrients

- Relevance: LOW

- As Found: Unknown

- ID: M16885

- Name: Trace Elements

- Relevance: LOW

- As Found: Unknown

- ID: M4278

- Name: Hypolipidemic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M28883

- Name: Lipid Regulating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M17412

- Name: Vasodilator Agents

- Relevance: LOW

- As Found: Unknown

- ID: T455

- Name: Nicotinamide

- Relevance: HIGH

- As Found: Continuing

- ID: T453

- Name: Niacin

- Relevance: HIGH

- As Found: Continuing

- ID: T454

- Name: Niacinamide

- Relevance: HIGH

- As Found: Continuing

- ID: T456

- Name: Nicotinic Acid

- Relevance: HIGH

- As Found: Continuing

- ID: T471

- Name: Vitamin B3

- Relevance: HIGH

- As Found: Continuing

- ID: T446

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T448

- Name: Folate

- Relevance: LOW

- As Found: Unknown

- ID: T475

- Name: Vitamin B9

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000009536

- Term: Niacinamide

- ID: D000009525

- Term: Niacin

- ID: D000009539

- Term: Nicotinic Acids

### Misc Info Module

- Version Holder: 2024-05-31
