Oral Contraceptive vs Menstrual Cycle Ex Vivo Model

Contraceptives, Oral Clinical Trial

— OCEV  

Official title:

The Effect of Menstrual Phase and Oral Contraceptives on Muscle Protein Metabolism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06124274
• Other study ID #: OCEV
• Status: Recruiting
• Phase: N/A
• Start date: August 9, 2023
• Est. completion date: September 1, 2024

Study information

• Verified date: November 2023
• Source: University of Toronto
• Contact: Daniel R Moore, PhD
• Phone: 4169464088
• Email: dr.moore[@]utoronto.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: September 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Contraceptives, Oral

Intervention

Behavioral:
• Protein tracer drink
Subjects will be fed a mixed-macronutrient beverage at rest (0.75g/kg lean body mass of carbohydrates; 0.125g/kg lean body mass of protein). Amino acid composition of the protein will be modelled off the composition of egg. Leucine content will be enriched to 5% with [13 Carbon(13C)]-leucine.

Locations

Country	Name	City	State
Canada	Goldring Centre for High Performance Sport at the University of Toronto	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University of Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Protein Synthesis (Murine Cell-Based Experiments, ex-vivo experiments)	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	60 minutes
Secondary	Whole-body protein synthesis	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).	6 hours
Secondary	Urinary Measures (Muscle Protein Breakdown)	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.	6 hours