Progesterone and Muscle Protein Synthesis in Premenopausal Women (MP4-MPS)

NCT07173361 | Not Yet Recruiting Phase 1

• 1 other identifier: MP4-MPS
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if micronized progesterone (PROMETRIUM®) influences the muscle-building response to resistance exercise in healthy premenopausal women aged 18-30 years. The main questions it aims to answer are:

• Take two oral doses of progesterone (400 mg total, 34 and 10 hours before testing) or placebo
• Complete a unilateral leg extension exercise session in the lab
• Receive an infusion of a stable isotope tracer and provide blood samples
• Undergo muscle biopsies from the exercised and rested legs

Conditions

Healthy Volunteers; Female; Progesterone; Premenopausal

Keywords

Progesterone; Muscle protein synthesis; Stable isotope tracer; Female physiology; Premenopausal females; Exercise metabolism; Micronized progesterone; Resistance exercise; Skeletal muscle

Outcome Measures

Primary Outcomes (1)

• Myofibrillar muscle protein synthesis (MPS) rate

  Incorporation of L-\[ring-¹³C₆\]-phenylalanine into myofibrillar proteins, measured via bilateral muscle biopsies (vastus lateralis, exercised vs. rested legs). The primary endpoint is the treatment (micronized progesterone vs. placebo) × leg (exercised vs. rested) interaction in MPS under fed conditions.

  5 hours after standardized feeding and unilateral resistance exercise (infusion period)

Secondary Outcomes (6)

• Myofibrillar MPS in rested leg (fed condition)

  5 hours after standardized feeding

• Myofibrillar MPS in rested leg (fasted condition)

  -240 to 0 minutes before feeding (fasted infusion period)

• Circulating serum progesterone concentrations (pharmacokinetics)

  -240 to 300 minutes (fasted and fed infusion periods)

• Postprandial amino acid response

  0 to 300 minutes after standardized feeding

• Plasma tracer enrichment verification

  Throughout infusion (-240 to 300 minutes)

Study Arms (2)

Experimental: Micronized Progesterone

EXPERIMENTAL

Drug - Micronized progesterone (oral capsules; 400 mg total as 2 × 200 mg at \~34 h and \~10 h pre-trial)

Drug: Micronized progesterone (oral capsules)

Placebo Comparator: Placebo

PLACEBO COMPARATOR

Drug - Placebo (oral capsules; matched schedule and appearance)

Drug: placebo capsule

Interventions

Micronized progesterone (oral capsules) DRUG

Two doses of 400 mg total micronized progesterone, administered as 2 × 200 mg capsules \~34 hours and \~10 hours prior to infusion trial, taken with a standardized nutritional drink.

Also known as: PROMETRIUM

Experimental: Micronized Progesterone

placebo capsule DRUG

Matched oral placebo capsules administered on the same schedule (\~34 and \~10 hours prior to infusion trial) with a standardized nutritional drink.

Placebo Comparator: Placebo

Eligibility Criteria

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

You may qualify if:

• Self-identifies as female and is assigned female at birth.
• Aged 18 to 30 years (inclusive).
• Body mass index (BMI) between 18 and 34.9 kg/m² (inclusive).
• In general, good health, as determined by a study-specific health screening questionnaire and medical history review.
• Reports regular menstrual cycles (21-35 days in length) for the past 3 consecutive months.
• Not currently using hormonal contraceptives and has completed a minimum 3-month washout period.
• Resting blood pressure \<140/90 mmHg at screening and on the infusion day.
• Willing and able to provide written informed consent in English.

You may not qualify if:

• Current use of tobacco, vaping products, or nicotine-containing substances.
• Ineligible for physical activity as determined by the Get Active Questionnaire (GAQ).
• Any medical, orthopedic, or psychiatric condition that, in the opinion of the Investigator, could interfere with the participant's ability to comply with study procedures or pose additional risk.
• Current gastrointestinal or swallowing disorders that may interfere with supplement ingestion (e.g., chronic diarrhea, regurgitation, dysphagia).
• Currently pregnant, planning to become pregnant, or known/suspected to be pregnant.
• Use of hormonal contraceptives within the past 3 months.
• Presence of any electronic medical devices or metallic implants that may interfere with DXA scanning or muscle biopsy procedures.
• History of neuromuscular disorders or muscle/bone wasting diseases.
• Current or recent use (within 3 months) of medications known to affect protein metabolism (e.g., glucocorticoids, systemic NSAIDs, isotretinoin, or anabolic agents).
• Personal or first-degree family history of thrombotic events (e.g., DVT, PE, stroke, myocardial infarction).
• Use of anticoagulant or antiplatelet medications.
• Excessive alcohol intake (\>21 units per week; 1 unit = 10 mL of pure ethanol).
• History of bleeding disorders or known coagulation or platelet abnormalities.
• Known hypersensitivity or allergy to micronized progesterone, soya, peanuts, or any excipients in the study capsule.
• History or current diagnosis of liver dysfunction or hepatic disease, unless liver function tests have returned to normal ranges.

Sponsors & Collaborators

• McMaster University: lead

Study Sites (1)

Exercise Metabolism Research Laboratory

Hamilton, Ontario, L8S 4K1, Canada

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

Central Study Contacts

Stuart Phillips, Ph.D.

CONTACT

905-525-9140; phillis@mcmaster.ca

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: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Parallel assignment with within-participant leg comparison. Participants are randomized 1:1 to micronized progesterone or matched placebo and complete the same unilateral resistance exercise and infusion protocol. Both groups receive identical procedures; only the study drug differs. The exercised leg serves as an internal comparator to the contralateral rested leg for physiologic endpoints (this is not a crossover). Randomization is computer-generated with concealed allocation; study staff, participants, and outcome assessors are blinded to assignment. Single-site conduct.

Study Record Dates

• First Submitted: September 7, 2025
• First Posted: September 15, 2025
• Study Start: September 15, 2025
• Primary Completion: December 15, 2025
• Study Completion: December 15, 2025
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)