Oral Contraceptive vs Menstrual Cycle Ex Vivo Model

Not Applicable

Recruiting

• Conditions: Contraceptives, Oral; Sex Hormone
• Interventions: Behavioral: Protein tracer drink

• Registration Number: NCT06124274
• Lead Sponsor: University of Toronto

Brief Summary

Despite comprising half the population, females are often left out of muscle research due to the impact of changing hormones during the menstrual cycle and when using oral contraceptives. This makes it hard to perform costly and invasive studies involving tracers to study muscle protein metabolism. Consequently, we lack a clear understanding of how these hormonal changes affect muscle growth.

There is a need for less invasive methods to study how sex hormones and oral contraceptives influence muscle protein metabolism. Ex vivo models, where serum from participants is applied to mouse muscle cell cultures, mimic the conditions of human muscle cells and can provide initial insights.

Detailed Description

The aim of the study is to develop a non-invasive model using serum from both oral contraceptive users and non-users at various stages of their cycles, to understand if different cycle or pill stages affect how muscles process proteins.

Study Timeline

• Study Start: 2023-08-09
• Study First Submitted: 2023-08-17
• Status Verified: 2023-11
• Study First Submitted QC: 2023-11-08
• Last Update Submitted: 2023-11-08
• Study First Posted: 2023-11-09
• Last Update Posted: 2023-11-09
• Primary Completion: 2024-09-01
• Study Completion: 2024-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 10

Inclusion Criteria

• BMI between 18.5-29.9 kg/m2 (I.e., non-obese).
• For OC users: on monophasic OCs for > 3 months prior to study enrollment
• For non-OC users: regular menstrual cycles length (25-35 days) for at least 3 months prior to study and at least 6 months off of OCs.

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Exclusion Criteria

• Chronic disease diagnosis (cardiovascular, thyroid, diabetes)
• Current or recent remission of cancer
• Regular use of NSAID (except low-dose aspirin), anticoagulants
• Use of prescription drugs that would impact metabolism, e.g. Statins, Lithium, Attention-Deficit/Hyperactivity Disorder (ADHD) medication.
• Insertion of intrauterine device (IUD) - exception: copper
• Use of ergogenic aids such as creatine
• Regular Tabacco use
• Use of illicit drugs (growth hormones, testosterone)
• For non-OC users: Use of oral contraceptives for > 6 months prior to study enrollment - to ensure return to regular menstrual cycle.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Active pill phase	Protein tracer drink	10-20 days after starting new pill cycle.
Withdrawal phase	Protein tracer drink	48hrs after last pill (during placebo pill phase).
Mid-Follicular Phase	Protein tracer drink	7-11 days after onset of menses.
Mid-Luteal Phase	Protein tracer drink	5-9 days after ovulation (as confirmed with ovulation test kits).

Primary Outcome Measures

Name	Time	Method
Protein Synthesis (Murine Cell-Based Experiments, ex-vivo experiments)	60 minutes	Investigators will use human serum obtained from fasted and fed timepoints (-15, 20, 40 and 60 minutes following beverage consumption) to condition cell culture media (20% volume). To determine the effects of using fasted and/or fed 'human-conditioned' culture media on cell protein synthesis, puromycin incorporation (measure of protein synthesis) will be measured via western blot and expressed relative to a no-serum control. A two-way repeated measures ANOVA will be used to analyze outcomes with cycle stage and group (OC vs non-OC) used as factors

Secondary Outcome Measures

Name	Time	Method
Whole-body protein synthesis	6 hours	Investigators will measure the enrichment of \[13 Carbon CO2 (13CO2)\] in the breath by isotope ratio mass spectrometry (IRMS) in atom percent excess (APE). The measurement of carbon dioxide production (VCO2) and stable isotope tracer enrichment in the breath allows for the assessment of the rate at which amino acids are used for energy (i.e., oxidized), rather than for protein synthesis (i.e., retained in the body) by calculating the fraction of expired CO2 that contains 13C. Leucine retention (umol/kg) will then be calculated from the difference between the known amount of leucine provided (ingested) and leucine oxidation (as determined from 13CO2 breath enrichment).
Urinary Measures (Muscle Protein Breakdown)	6 hours	Investigators will measure urinary 3-methylhistidine (3MH) as an indirect marker of muscle protein breakdown over the course of the trial (6 hours) through pooled urine collection vs baseline urine.

Trial Locations

Locations (1)

Goldring Centre for High Performance Sport at the University of Toronto; 🇨🇦 Toronto, Ontario, Canada