Acute Effects of Progesterone on LH Pulses During the Follicular Phase (CRM006)

NCT01602679 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 16085R01HD058671
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Female Reproductive Physiology

Outcome Measures

Primary Outcomes (1)

• Change in Number of LH Pulses Per Hour

  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

  10 hours following administration of micronized progesterone or placebo

Secondary Outcomes (2)

• Change in Mean LH

  10 hours following administration of micronized progesterone or placebo

• Change in Mean LH Amplitude

  10 hours following administration of micronized progesterone or placebo

Study Arms (2)

micronized progesterone, then placebo

EXPERIMENTAL

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).

Drug: oral micronized progesterone suspension; Drug: Placebo

Placebo, then micronized progesterone

PLACEBO COMPARATOR

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

Drug: oral micronized progesterone suspension; Drug: Placebo

Interventions

oral micronized progesterone suspension DRUG

oral micronized progesterone (100 mg p.o.) suspension

Also known as: Progesterone

Placebo, then micronized progesterone; micronized progesterone, then placebo

Placebo DRUG

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

Placebo, then micronized progesterone; micronized progesterone, then placebo

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Virginia: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Center for Research in Reproduction

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Interventions

Progesterone

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Results Point of Contact

• Title: Dr. Christopher R. McCartney
• Organization: University of Virginia Center for Research in Reproduction

cm2hq@virginia.edu

4342430329

Study Officials

• Christopher R. McCartney, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Randomized, placebo-controlled, crossover study

Study Record Dates

• First Submitted: May 17, 2012
• First Posted: May 21, 2012
• Study Start: May 1, 2012
• Primary Completion: July 31, 2015
• Study Completion: July 31, 2015
• Last Updated: October 16, 2018
• Results First Posted: October 16, 2018

Record last verified: 2018-10

Locations

US (1)