Progesterone for Postpartum Cocaine Relapse

The investigators propose a placebo-controlled, randomized clinical trial that would enroll 50 postpartum women with a history of cocaine abuse or dependence to assess whether progesterone (100mgs twice daily) decreases postpartum cocaine use.

Study Overview

• Status: Completed
• Conditions: Cocaine Dependence; Cocaine Abuse
• Intervention / Treatment: Other: Placebo; Drug: Progesterone

Detailed Description

Specific Aim 1: To evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo.

Hypothesis 1: Compared to women who are randomized to placebo, those assigned to progesterone will use less cocaine as measured by urine toxicology results and self-reported days of use.

Specific aim 2: To obtain information about the safety and tolerability of progesterone treatment in the postpartum period.

Hypothesis 2: Side effects for progesterone will be similar to those of placebo.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Gravidas (women who delivered a baby in the past 12 weeks) who are 18 or older are eligible to participate.
• Women must meet diagnostic criteria for abuse or dependence of cocaine in the six-months prior to conception or during pregnancy.
• Women who abuse other illicit substances or alcohol would also be eligible as long as cocaine was their primary drug of abuse. If women are also opiate dependent, they must be undergoing treatment with methadone or buprenorphine. While we propose to target cocaine we will also monitor the ability of women with polysubstance use to maintain abstinence from substances other than cocaine.

Exclusion Criteria:

Women will be ineligible for the trial if they:

1. have a history of major medical illnesses including liver diseases, suspected or known malignancy, thrombophlebitis, deep vein thrombosis, pulmonary embolus, clotting or bleeding disorders, heart disease, diabetes, history of stroke or other medical conditions that the physician investigator deems as contraindicated for participation in the study;
2. have a known allergy to progesterone or peanuts (vehicle for micronized progesterone);
3. speak a language other than English;
4. are planning on moving out of the area in the first six months after delivery;
5. are unable to understand the study or are unable to provide informed consent;
6. are currently undergoing treatment with another pharmacological agent for substance abuse treatment (with the exception of methadone or buprenorphine as above);
7. have pending incarceration;
8. are currently incarcerated;
9. are using another progestin;
10. are unwilling to accept randomization;
11. are unwilling to use a barrier method of birth control for the duration of the study to ensure that they will not become pregnant.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matched placebo pills to be taken twice daily	Other: Placebo; Matched placebo pills to be taken twice daily
Experimental: Progesterone; 100 mgs progesterone twice daily	Drug: Progesterone; 100mgs progesterone twice daily; Other Names: prometrium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of Days Per Week of Cocaine Use	Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Measured by self-reported days of cocaine use per week via substance use calendar.	Weekly measurements, Baseline to 12 weeks
Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up	Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Measured by self-reported days of cocaine use per week during the trial period and during 3 month follow up using the substance use calendar	baseline, end of trial (week 12), 3-month post-trial follow-up
Proportion of Positive Urine Samples Per Week	Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Urine tox tests obtained qualitative and quantitative data on cocaine metabolites and other substances.	weekly measurements, baseline to 12 weeks
Proportion of Positive Urine Samples Per Week	Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Urine tox tests obtained qualitative and quantitative data on cocaine metabolites and other substances.	baseline, end of trial (week 12) and 3-month post-trial follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Comparison of Adverse Events Between Women in Placebo and Progesterone Group	To obtain information about the safety and tolerability of progesterone treatment in the postpartum period, women were queried at every visit about onset of adverse events, their seriousness, and their relatedness to study medication. Such data was monitored in SAETRS.	12 weeks postpartum
Cocaine Craving (Measured Weekly Using CCQ-Brief)	CCQ-Brief is a ten-item questionnaire developed from the 45-item CCQ. Each item is scored on a visual analogue scale ranging from 1-7, and items are averaged to yield a score from 1 to 7. Higher scores indicate stronger cocaine cravings.	baseline to 12 weeks
Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS))	EPDS scores were measured to detect depression as a possible adverse event and compare scores between the two groups. The scale consists of 10 items. Each item is scored from 0 to 3, and the 10 items are summed to calculate a total score with a possible range of 0 to 30 and higher scores indicating more severe depression.	baseline to 12 weeks
Salivary Progesterone Concentrations	A comparison of salivary progesterone concentrations across all samples for all timepoints	week 2, week 6, week 10, week 12

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Kimberly A Yonkers, MD, Yale School of Medicine; Principal Investigator: Mehmet Sofuoglu, MD, PhD, Yale School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: November 22, 2010
• First Submitted That Met QC Criteria: November 24, 2010
• First Posted (Estimate): November 29, 2010

Study Record Updates

• Last Update Posted (Actual): March 28, 2017
• Last Update Submitted That Met QC Criteria: February 24, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: cocaine dependence; postpartum period; cocaine abuse
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 1005006793; R21DA029914 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data request should be made to the PI