## Protocol Section
### Identification Module
**NCT ID:** NCT01602679

**Brief Title:** Acute Effects of Progesterone on LH Pulses During the Follicular Phase (CRM006)

**Official Title:** Acute Effects of Progesterone on LH Pulses During the Follicular Phase

#### Organization Study ID Info
**ID:** 16085
#### Organization
**Class:** OTHER
**Full Name:** University of Virginia
#### Secondary ID Infos
**ID:** R01HD058671
**Link:** https://reporter.nih.gov/quickSearch/R01HD058671
**Type:** NIH
### Status Module
#### Completion Date
**Date:** 2015-07-31

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2018-10-16

**Type:** ACTUAL

**Last Update Submit Date:** 2018-10-15

**Overall Status:** TERMINATED

#### Primary Completion Date
**Date:** 2015-07-31

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2018-10-16

**Type:** ACTUAL

**Results First Submit Date:** 2018-07-31

**Results First Submit QC Date:** 2018-10-15

#### Start Date
**Date:** 2012-05

**Status Verified Date:** 2018-10

#### Study First Post Date
**Date:** 2012-05-21
**Type:** ESTIMATED
**Study First Submit Date:** 2012-05-17
**Study First Submit QC Date:** 2012-05-18
**Why Stopped:** Interim analysis suggested futility.
### Sponsor Collaborators Module

#### Collaborators

**Class:** NIH

**Name:** Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Virginia

#### Responsible Party

**Investigator Affiliation:** University of Virginia

**Investigator Full Name:** Chris McCartney

**Investigator Title:** Associate Professor of Medicine

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The rapidity with which progesterone slows LH (and by inference GnRH) pulse frequency in women is unclear. The investigators hypothesize that progesterone slows LH pulse frequency within 10 hours. The investigators propose to assess this further with a randomized, cross-over, placebo-controlled study. Regularly cycling women without hyperandrogenism will be admitted to the Clinical Research Unit on cycle day 5-9 (mid-follicular phase) for a 10 hour frequent sampling study to observe LH, FSH, estradiol, progesterone, and testosterone. Either oral micronized progesterone suspension or placebo will be administered at 0900 h. During a subsequent menstrual cycle, subjects will undergo another study identical to the first except that oral progesterone will be exchanged for placebo or vice versa in accordance with a crossover design.

**Detailed Description:** The rapidity with which progesterone slows LH (and by inference GnRH) pulse frequency in women is unclear. The investigators hypothesize that progesterone slows LH pulse frequency within 10 hours. The investigators propose to assess this further with a randomized, cross-over, placebo-controlled study. Regularly cycling women without hyperandrogenism will be admitted to the Clinical Research Unit on cycle day 5-9 (mid-follicular phase) for a frequent sampling study. Beginning at 0900 h, blood for LH, FSH, estradiol, progesterone, and testosterone will be obtained over a 10-hour period. Either oral micronized progesterone (100 mg p.o.) suspension or placebo will be administered at 0900 h. During a subsequent menstrual cycle, subjects will undergo another study identical to the first except that oral progesterone will be exchanged for placebo or vice versa in accordance with a crossover design. The primary endpoint of interest is LH pulse frequency; the investigators will compare LH pulse frequency after progesterone administration to LH pulse frequency after placebo administration.

### Conditions Module

**Conditions:**

- Female Reproductive Physiology

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** Randomized, placebo-controlled, crossover study

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 12

**Type:** ACTUAL

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants first received oral micronized progesterone (100 mg p.o.) suspension. After a washout period of approximately 20 days, they then received placebo (matching oral micronized progesterone suspension).

**Intervention Names:**

- Drug: oral micronized progesterone suspension

- Drug: Placebo

**Label:** micronized progesterone, then placebo

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants first received placebo. After a washout period of approximately 20 days, they then received oral micronized progesterone syrup (100 mg p.o.)Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

**Intervention Names:**

- Drug: oral micronized progesterone suspension

- Drug: Placebo

**Label:** Placebo, then micronized progesterone

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Placebo, then micronized progesterone

- micronized progesterone, then placebo

**Description:** oral micronized progesterone (100 mg p.o.) suspension

**Name:** oral micronized progesterone suspension

**Other Names:**

- Progesterone

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo, then micronized progesterone

- micronized progesterone, then placebo

**Description:** Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** The primary endpoint is the change in the number of LH pulses per hour (over 10 h), comparing (a) number of LH pulses at baseline to (b) number of LH pulses immediately after progesterone or placebo administration

**Measure:** Change in Number of LH Pulses Per Hour

**Time Frame:** 10 hours following administration of micronized progesterone or placebo

#### Secondary Outcomes

**Description:** This secondary endpoint is the change of the mean LH (over 10 h), comparing (a) mean LH at baseline to (b) mean LH immediately after progesterone or placebo administration

**Measure:** Change in Mean LH

**Time Frame:** 10 hours following administration of micronized progesterone or placebo

**Description:** This secondary endpoint is the change in the mean LH amplitude (over 10 h), comparing (a) mean LH amplitude at baseline to (b) mean LH amplitude immediately after progesterone or placebo administration

**Measure:** Change in Mean LH Amplitude

**Time Frame:** 10 hours following administration of micronized progesterone or placebo

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Subjects will be healthy women with regular menstrual cycles and no evidence of hyperandrogenism.
* Subjects will be 18-30 years old; the investigators use a cutoff age of 30 years because age-related alterations in the hypothalamic-pituitary-ovarian axis is uncommon before age 30 years.
* Subjects will be willing to strictly avoid pregnancy (using non-hormonal methods) during the time of study and must be willing and able to provide informed consent.

Exclusion Criteria:

* Pregnancy
* Lactation
* History of allergy to progesterone
* BMI \< 18 kg/m2 or \> 30 kg/m2 (underweight and obesity can affect hypothalamic-pituitary-ovarian function)
* Excessive exercise, defined as routine and current engagement in either (a) moderate exercise (e.g., brisk walking) exceeding 14 hours per week or (a) vigorous exercise exceeding 7 hours a week.
* Clinical hyperandrogenism (primarily hirsutism)
* Abnormally elevated free testosterone or DHEAS concentration
* A previous diagnosis of diabetes, a fasting glucose ≥ 126 mg/dl
* Abnormal TSH (subjects with adequately treated hypothyroidism, reflected by normal TSH values, will not be excluded; or, for a new diagnosis of hypothyroidism, further study will at the least be delayed pending appropriate treatment) (confirmed on repeat)
* Abnormal prolactin (confirmed on repeat)
* Evidence of Cushing's syndrome by history or physical exam
* History of venous thromboembolism, breast/ovarian/endometrial cancer
* The investigators will exclude women with any other cancer diagnosis and/or treatment (with the exception of basal cell or squamous skin carcinoma) unless they have remained clinically disease free (based on appropriate surveillance) for five years.
* Women with anemia (hematocrit \< 36% and hemoglobin level \< 12 g/dl) will be treated with iron for a maximum of 2 sequential months before the 1st admission and/or before the 2nd admission. If they remain anemic after 2 sequential months of ferrous gluconate (325 mg bid), they will then be excluded from further participation in the study.
* Women with a significant history of cardiac or pulmonary dysfunction (e.g., known or suspected congestive heart failure; known or suspected coronary atherosclerosis; asthma requiring systemic intermittent corticosteroids; etc.) will be excluded.
* Women with liver enzymes, alkaline phosphatase, or bilirubin \> 1.5 times upper limit of normal (confirmed on repeat) will be excluded, with the exception that mild bilirubin elevations will be accepted in the setting of known Gilbert's syndrome.
* Abnormal sodium or potassium concentrations (confirmed on repeat); bicarbonate concentrations \<20 or \>30 (confirmed on repeat)
* Women with abnormal renal function (i.e., serum creatinine \> 1.4) will be excluded (confirmed on repeat)
* Due to the amount of blood being drawn in the study, subjects with body weight \< 110 pounds will be excluded from the study
* Being a study of the acute effects of progesterone on the hypothalamic-pituitary unit, subjects must not take hormonal medications (e.g., oral contraceptives) or other medications known to affect the reproductive axis for 60 days prior to the study and during the study.

**Healthy Volunteers:** True

**Maximum Age:** 30 Years

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Charlottesville

**Country:** United States

**Facility:** Center for Research in Reproduction

**State:** Virginia

**Zip:** 22908

#### Overall Officials

**Official 1:**

**Affiliation:** University of Virginia

**Name:** Christopher R. McCartney, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Description:** We do not have current plans to share IPD

**IPD Sharing:** UNDECIDED

## Document Section

### Large Document Module

#### Large Docs

- Date: 2014-09-24

- Filename: Prot_SAP_000.pdf

- Has ICF: False

- Has Protocol: True

- Has SAP: True

- Label: Study Protocol and Statistical Analysis Plan

- Size: 1004760

- Type Abbrev: Prot_SAP

- Upload Date: 2018-07-03T15:29

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: Rare

- Name: Rare Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Ancestors

- ID: D000011372

- Term: Progestins

- ID: D000006728

- Term: Hormones

- ID: D000006730

- Term: Hormones, Hormone Substitutes, and Hormone Antagonists

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M14245

- Name: Progesterone

- Relevance: HIGH

- As Found: Chinese

- ID: M14244

- Name: Progestins

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M9788

- Name: Hormone Antagonists

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000011374

- Term: Progesterone

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** Oral Micronized Progesterone Suspension

**Deaths Num At Risk:** 4

**Description:** Oral micronized progesterone (100 mg) suspension

**ID:** EG000

**Other Num Affected:** 1

**Other Num at Risk:** 4

**Serious Number At Risk:** 4

**Title:** Oral Micronized Progesterone Suspension

**Group ID:** EG001

**Title:** Placebo

**Deaths Num At Risk:** 3

**Description:** Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

**ID:** EG001

**Other Num at Risk:** 3

**Serious Number At Risk:** 3

**Title:** Placebo

**Frequency Threshold:** 0

#### Other Events

**Term:** Irregular Menstrual Bleeding

**Assessment Type:** NON_SYSTEMATIC_ASSESSMENT

**Notes:** Temporary spotting

**Organ System:** Reproductive system and breast disorders

**Source Vocabulary:** 

**Time Frame:** From start of study procedures until end of study participation, up to 6 months

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 4

**Group ID:** BG001

**Value:** 3

**Group ID:** BG002

**Value:** 7

**Units:** Participants

### Group

**ID:** BG000

**Title:** Oral Micronized Progesterone Suspension, Then Placebo

**Description:** Participants first received oral micronized progesterone (100 mg p.o.) suspension. After a washout period of approximately 20 days, they then received Placebo.

oral micronized progesterone suspension: oral micronized progesterone (100 mg p.o.) suspension Placebo: Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

### Group

**ID:** BG001

**Title:** Placebo, Then Oral Micronized Progesterone Suspension

**Description:** Participants first received Placebo. After a washout period of approximately 20 days, they then received oral micronized progesterone suspension. Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

Placebo: Placebo contains only inert ingredients and is not expected to exert any direct physiological effects oral micronized progesterone suspension: oral micronized progesterone (100 mg p.o.) suspension

### Group

**ID:** BG002

**Title:** Total

**Description:** Total of all reporting groups

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**Category Title:** <=18 years

#### Measurement

**Group ID:** BG000

**Value:** 4

#### Measurement

**Group ID:** BG001

**Value:** 3

#### Measurement

**Group ID:** BG002

**Value:** 7

**Category Title:** Between 18 and 65 years

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**Category Title:** >=65 years

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 4

#### Measurement

**Group ID:** BG001

**Value:** 3

#### Measurement

**Group ID:** BG002

**Value:** 7

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**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:** American Indian or Alaska Native

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**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:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

**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:** 4

#### Measurement

**Group ID:** BG001

**Value:** 3

#### Measurement

**Group ID:** BG002

**Value:** 7

**Category Title:** Unknown or Not Reported

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 4

#### Measurement

**Group ID:** BG001

**Value:** 3

#### Measurement

**Group ID:** BG002

**Value:** 7

**Class Title:** United States

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Age, Categorical
**Unit of Measure:** Participants
### Measure 2
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Race (NIH/OMB)
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** NUMBER
**Title:** Region of Enrollment
**Unit of Measure:** participants
## Results Section - More Information Module
### Certain Agreement
### Point of Contact
**Email:** cm2hq@virginia.edu
**Organization:** University of Virginia Center for Research in Reproduction
**Phone:** 4342430329
**Title:** Dr. Christopher R. McCartney
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
### Outcome Measure 3
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 0.28
- **Upper Limit:** 
- **Value:** 0.77
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.35
- **Upper Limit:** 
- **Value:** 0.79
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 2.2
- **Upper Limit:** 
- **Value:** 5.8
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 2.3
- **Upper Limit:** 
- **Value:** 4.6
**Title:** 
#### Outcome Measure 3
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 2.8
- **Upper Limit:** 
- **Value:** 4.3
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 2.8
- **Upper Limit:** 
- **Value:** 3.6
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** The primary endpoint is the change in the number of LH pulses per hour (over 10 h), comparing (a) number of LH pulses at baseline to (b) number of LH pulses immediately after progesterone or placebo administration
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 10 hours following administration of micronized progesterone or placebo
**Title:** Change in Number of LH Pulses Per Hour
**Type:** PRIMARY
**Unit of Measure:** pulses/h
##### Group
**Description:** oral micronized progesterone (100 mg p.o.) suspension

oral micronized progesterone suspension: oral micronized progesterone (100 mg p.o.) suspension
**ID:** OG000
**Title:** Oral Micronized Progesterone Suspension
##### Group
**Description:** Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

Placebo: Placebo contains only inert ingredients and is not expected to exert any direct physiological effects
**ID:** OG001
**Title:** Placebo
#### Outcome Measure 2
**Description:** This secondary endpoint is the change of the mean LH (over 10 h), comparing (a) mean LH at baseline to (b) mean LH immediately after progesterone or placebo administration
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 10 hours following administration of micronized progesterone or placebo
**Title:** Change in Mean LH
**Type:** SECONDARY
**Unit of Measure:** IU/L
##### Group
**Description:** oral micronized progesterone (100 mg p.o.) suspension

oral micronized progesterone suspension: oral micronized progesterone (100 mg p.o.) suspension
**ID:** OG000
**Title:** Oral Micronized Progesterone Suspension
##### Group
**Description:** Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

Placebo: Placebo contains only inert ingredients and is not expected to exert any direct physiological effects
**ID:** OG001
**Title:** Placebo
#### Outcome Measure 3
**Description:** This secondary endpoint is the change in the mean LH amplitude (over 10 h), comparing (a) mean LH amplitude at baseline to (b) mean LH amplitude immediately after progesterone or placebo administration
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Reporting Status:** POSTED
**Time Frame:** 10 hours following administration of micronized progesterone or placebo
**Title:** Change in Mean LH Amplitude
**Type:** SECONDARY
**Unit of Measure:** IU/L
##### Group
**Description:** oral micronized progesterone (100 mg p.o.) suspension

oral micronized progesterone suspension: oral micronized progesterone (100 mg p.o.) suspension
**ID:** OG000
**Title:** Oral Micronized Progesterone Suspension
##### Group
**Description:** Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

Placebo: Placebo contains only inert ingredients and is not expected to exert any direct physiological effects
**ID:** OG001
**Title:** Placebo
### Participant Flow Module
#### Group
**Description:** Participants first received oral micronized progesterone (100 mg p.o.) suspension. After a washout period of approximately 20 days, they then received placebo.

oral micronized progesterone suspension: oral micronized progesterone (100 mg p.o.) suspension
**ID:** FG000
**Title:** Oral Micronized Progesterone Suspension, Then Placebo
#### Group
**Description:** Participants first received Placebo. After a washout period of approximately 20 days, they then received oral micronized progesterone suspension. Placebo contains only inert ingredients and is not expected to exert any direct physiological effects

Placebo: Placebo contains only inert ingredients and is not expected to exert any direct physiological effects
**ID:** FG001
**Title:** Placebo, Then Oral Micronized Progesterone Suspension
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 4
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 3
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 4
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 3
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
**Pre-Assignment Details:** 12 subjects enrolled in this study. 5 subjects completed screening procedures only (these 5 subjects were withdrawn from study prior to being assigned to an arm of intervention).
**Has Results:** True