Oral Contraceptives for Treating Premenstrual Dysphoric Disorder in Bipolar Disorder

A Pilot, Randomized, Placebo-Controlled Trial Evaluating the Treatment of Premenstrual Dysphoric Disorder With Oral Contraceptives in Bipolar Disorder.

This study is a pilot, randomized, placebo-controlled trial evaluating the treatment of Premenstrual Dysphoric Disorder comorbid with Bipolar Disorder using combined oral contraceptives.

Lay Summary:

This study is being done with the hope of finding a safe and effective treatment for individuals who experience both bipolar disorder and severe premenstrual symptoms. As part of this clinical trial, participants will receive either a combined oral contraceptive (i.e. oral birth control pills) as a treatment for severe premenstrual symptoms or a placebo (a pill without any active components - similar to a sugar pill). People that are enrolled in this study will either receive the treatment or the placebo for a period of 90 days. During this time, people that are participating in the study will fill out some questionnaires, and their mental and physical health will be monitored by the study physicians.

One of the goals of this study is to also understand whether it is feasible (practical) to do a larger clinical trial using this treatment in this group of people.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Disorder; Premenstrual Dysphoric Disorder
• Intervention / Treatment: Drug: Yaz; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Benicio N Frey, MD, MSc, PhD; Phone Number: 33605 (905)522-1155; Email: freybn@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3K7
      • Recruiting
      • St Joseph's Healthcare Hamilton
      • Contact: Benicio N Frey, MD, MSc, PhD; Phone Number: 33605 (905)522-1155; Email: freybn@mcmaster.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 16-45 years of age
• Diagnosis of BD (clinically euthymic) according to the DSM-5
• Diagnosis of PMDD according to the DSM-5
• Regular menstrual cycles
• No contraindication to use oral contraceptives
• Capable of consent for treatment

Exclusion Criteria:

• Smoking and over the age of 35
• Current or recent (last month) use of systemic estrogen or progesterone treatment
• Severe reactions to hormone treatment
• Pregnant or breastfeeding
• Current substance use disorder
• Oophorectomy or hysterectomy
• Current unstable medical conditions
• History of current or past breast cancer, pancreatitis, migraines or blood clotting disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combined oral contraceptive (3mg drospirenone/ 0.02mg ethinyl estradiol); Continuous treatment with 3mg drospirenone/ 0.02mg ethinyl estradiol for 12 weeks	Drug: Yaz; Continuous treatment with 3mg drospirenone/ 0.02mg ethinyl estradiol for 12 weeks; Other Names: 3mg drospirenone/ 0.02mg ethinyl estradiol
Placebo Comparator: Placebo; Continuous treatment with placebo for 12 weeks	Drug: Placebo; Appearance, packaging, and labeling of placebo will be matched to their active counterpart.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility outcome: treatment compliance	Treatment compliance - assessed via number and percentage of treatment pills taken	12 weeks
Feasibility outcome: retention rates	Retention rates - number and percentage of people who remain in the study once randomized	12 weeks
Feasibility outcome: recruitment rate (monthly)	Recruitment rate (monthly) - number of participants per month	2 years
Feasibility outcome: recruitment capacity	Recruitment capacity - total number of participants randomized and enrolled	2 years
Feasibility outcome: screening rates (monthly)	Screening rates (monthly) - number screened; number enrolled as a percentage of number screened	2 years
Feasibility outcome: duration of assessment process	Duration of assessment process - mean in hours from start to finish for each visit	Screening
Feasibility outcome: duration of assessment process	Duration of assessment process - mean in hours from start to finish for each visit	Baseline
Feasibility outcome: duration of assessment process	Duration of assessment process - mean in hours from start to finish for each visit	Week 4
Feasibility outcome: duration of assessment process	Duration of assessment process - mean in hours from start to finish for each visit	Week 8
Feasibility outcome: duration of assessment process	Duration of assessment process - mean in hours from start to finish for each visit	Week 12
Feasibility outcome: safety of use of oral contraceptives in this population	Safety of use of oral contraceptives in this population - adverse events reported, onset of mood episodes (assessed by clinicians)	Week 4
Feasibility outcome: safety of use of oral contraceptives in this population	Safety of use of oral contraceptives in this population - adverse events reported, onset of mood episodes (assessed by clinicians)	Week 8
Feasibility outcome: safety of use of oral contraceptives in this population	Safety of use of oral contraceptives in this population - adverse events reported, onset of mood episodes (assessed by clinicians)	Week 12
Feasibility outcome: tolerability	Tolerability - assessed as percentage dropped out after randomization due to adverse events	Week 4
Feasibility outcome: tolerability	Tolerability - assessed as percentage dropped out after randomization due to adverse events	Week 8
Feasibility outcome: tolerability	Tolerability - assessed as percentage dropped out after randomization due to adverse events	Week 12
Feasibility outcome: response rates	Response rates - response will be defined as 50% decrease from baseline symptom change from late luteal to follicular phase; remission will be defined as number and percentage of responders who no longer need DSM-5 criteria for PMDD	Week 12
Feasibility outcome: estimated treatment effect	Estimated treatment effect - mean percent change from baseline to post-treatment in percent change on the MAC-PMSS from late luteal to follicular phase	Week 12
Feasibility outcome: variance of the treatment effect	Variance of the treatment effect - standard deviation of above measure.	Week 12

Collaborators and Investigators

• Sponsor: St. Joseph's Healthcare Hamilton
• Collaborators: McMaster University; Hamilton Academic Health Sciences Organization
• Investigators: Principal Investigator: Benicio N Frey, MD, MSc,PhD, St. Joseph's Healthcare Hamilton

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2022
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: July 14, 2021
• First Submitted That Met QC Criteria: October 18, 2021
• First Posted (Actual): October 28, 2021

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: bipolar disorder; premenstrual dysphoric disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Mood Disorders; Bipolar and Related Disorders; Depressive Disorder; Menstruation Disturbances; Premenstrual Syndrome; Bipolar Disorder; Premenstrual Dysphoric Disorder; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Natriuretic Agents; Diuretics; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Hormonal; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Estradiol; Ethinyl Estradiol; Drospirenone
• Other Study ID Numbers: BDPMDD01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No