Progesterone for Postpartum Cocaine Relapse

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Progesterone for Postpartum Cocaine Relapse

Conditions
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Cocaine Abuse, Cocaine Dependence

Intervention / Treatment
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* Drug: Progesterone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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: 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; have a known allergy to progesterone or peanuts (vehicle for micronized progesterone); speak a language other than English; are planning on moving out of the area in the first six months after delivery; are unable to understand the study or are unable to provide informed consent; are currently undergoing treatment with another pharmacological agent for substance abuse treatment (with the exception of methadone or buprenorphine as above); have pending incarceration; are currently incarcerated; are using another progestin; are unwilling to accept randomization; are unwilling to use a barrier method of birth control for the duration of the study to ensure that they will not become pregnant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matched placebo pills to be taken twice daily | Other: Placebo<br>* Matched placebo pills to be taken twice daily<br>|
| Experimental: Progesterone<br>100 mgs progesterone twice daily | Drug: Progesterone<br>* 100mgs progesterone twice daily<br>* Other names: prometrium;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cocaine abuse, cocaine dependence, postpartum period