Progesterone for the Treatment of Cocaine Dependence - 1

Study Overview
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Brief Summary
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Past research has demonstrated that cocaine dependent women experience less severe responses to cocaine during the luteal phase of the menstrual cycle, when estrogen and progesterone concentrations are high. The purpose of this study is to determine whether administered progesterone reduces subjective and physiological responses to cocaine in cocaine dependent individuals.

Detailed Description
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Changes in ovarian hormones across the menstrual cycle impact responses to cocaine in women. Studies have shown that cocaine's effects are dampened during the luteal phase of the menstrual cycle, when estrogen and progesterone concentrations are high, relative to the other phases of the cycle, when concentrations of these hormones are relatively low. The purpose of this study is to determine whether progesterone reduces subjective and physiological responses to cocaine in cocaine dependent individuals. In addition, this study will help to advance the possibility of hormonal progesterone and pharmacologically-related drugs as potential treatment components for cocaine abuse. Participants will undergo two 4-day inpatient periods, totaling 8 days of treatment. For women, the inpatient periods will occur during two consecutive menstrual cycles; for men, these will occur during two consecutive months. On Day 1, participants will receive a first dose of either progesterone or placebo. On Day 2, participants will receive a second and third dose of study medication. Participants will also participate in an adaptation session, which will familiarize the participant with the smoking equipment that will be used the following day. On Day 3, participants will receive a fourth dose of medication 2 hours prior to a smoking lab session. Prior to beginning the smoking lab session, participants will be asked to rate their current cocaine craving, anxiety level, appetite, and premenstrual symptoms. Participants will then be given a sample of the cocaine dose for the given day. During the smoking lab session, participants will be asked additional cocaine craving questions at pre-determined intervals and will be given the option to trade in previously earned tokens for either money or a dose of cocaine. Following completion of the smoking lab session, participants will receive their fifth dose of medication.

Official Title
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Interactions Between Progesterone and Cocaine in Women

Conditions
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Cocaine Abuse, Cocaine-Related Disorders

Intervention / Treatment
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* Drug: Progesterone
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Smoked at least 1 gram of cocaine each week for the 6 months prior to study entry Agrees to use an adequate method of contraception for the duration of the study If female, current regular menses Exclusion Criteria: Major psychiatric illnesses, including psychotic mood and anxiety disorders Current dependence on alcohol or drugs other that cocaine or nicotine History of major medical illnesses, including liver disease, abnormal vaginal bleeding, suspected or known breast cancer, thrombophlebitis, or other medical conditions Current use of oral contraceptives or other types of hormonal contraceptives Amenorrhea Currently on parole or probation Received treatment for chemical dependency within the 6 months prior to study entry Known allergy to progesterone or peanuts

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 46 Years

Sexes Eligible for Study
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All

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: Crossover Assignment
Interventional Model Description: Participants will be randomized to receive either progesterone or placebo during month 1, then crossover in month 2. During each month, participants will be randomized to receive either an active or inactive dose of cocaine during a 4-day in-hospital testing visit for a total of 4 testing days with self-administered cocaine.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Progesterone<br>200mg progesterone twice daily | Drug: Progesterone<br>* 200mg progesterone twice daily<br>* Other names: prometrium;|
| Placebo Comparator: Placebo<br>Placebo twice daily | Other: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decision to Self-Administer Cocaine | During 1 inpatient testing day, participants were given the opportunity to spend 5 earned tokens on either an active dose of cocaine or to keep the tokens for a $5 reward for each token. Decisions were solicited every 30 minutes. Outcome measure is reported as the percent of 5 decisions for which the participant chose to self-administer cocaine. 0% indicates that all 5 tokens were retained and traded for monetary reward. 100% indicates that the participant spent all 5 tokens on cocaine for self-administration. On another inpatient day, participants were offered the same 5 choices but with a inactive dose of cocaine (amount of cocaine insufficient for psychoactive effect) or a $5 monetary reward. 0% indicates that all 5 tokens were retained and traded for monetary reward. 100% indicates that the participant spent all 5 tokens on inactive doses of cocaine for self-administration. The order of days (active or inactive cocaine dosage) was random. | 4 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate | During 1 inpatient testing day, participants were given the opportunity to spend 5 tokens on either an active dose of cocaine or to keep the tokens for a $5 reward each. Decisions were solicited every 30 minutes. There was a total of 5 decisions solicited. On another inpatient day, participants were offered the same 5 choices but with a inactive dose of cocaine or a monetary reward. The order of days (active or inactive cocaine dosage) was random. These 2 testing days were completed during a 4-day in-hospital testing session under the progesterone condition and placebo condition. Order of progesterone and placebo conditions were randomized. Heart rate was taken 2.5 minutes following administration of cocaine (active or inactive dosage). Up to 5 HR measurements were recorded based on participant decision to self-administer cocaine or not. Mean across up to 5 measures was calculated. Outcome is reported as the mean of mean measures during each of 4 study conditions. | 4 days | 
| Systolic Blood Pressure | During 1 inpatient testing day, participants were given the opportunity to spend 5 tokens on either an active dose of cocaine or to keep the tokens for a $5 reward each. Decisions were solicited every 30 minutes. There was a total of 5 decisions solicited. On another inpatient day, participants were offered the same 5 choices but with a inactive dose of cocaine or a monetary reward. The order of days (active or inactive cocaine dosage) was random. These 2 testing days were completed during a 4-day in-hospital testing session under the progesterone condition and placebo condition. Progesterone and placebo conditions were randomized. Blood pressure was taken 2.5 minutes following administration of cocaine (active or inactive dosage). Up to 5 BP measurements were recorded based on participant decision to self-administer cocaine or not. Mean across up to 5 measures was calculated. Outcome is reported as the mean of mean measures during each of 4 study conditions. | 4 days | 
| Diastolic Blood Pressure | During 1 inpatient testing day, participants were given the opportunity to spend 5 tokens on either an active dose of cocaine or to keep the tokens for a $5 reward each. Decisions were solicited every 30 minutes. There was a total of 5 decisions solicited. On another inpatient day, participants were offered the same 5 choices but with a inactive dose of cocaine or a monetary reward. The order of days (active or inactive cocaine dosage) was random. These 2 testing days were completed during a 4-day in-hospital testing session under the progesterone condition and placebo condition. Progesterone and placebo conditions were randomized. Blood pressure was taken 2.5 minutes following administration of cocaine (active or inactive dosage). Up to 5 BP measurements were recorded based on participant decision to self-administer cocaine or not. Mean across up to 5 measures was calculated. Outcome is reported as the mean of mean measures during each of 4 study conditions. | 4 days | 
| Cocaine Craving | During 1 inpatient testing day, participants were given the opportunity to spend 5 tokens on either an active dose of cocaine or to keep the tokens for a $5 reward each. Decisions were solicited every 30 minutes. There was a total of 5 decisions solicited. On another inpatient day, participants were offered the same 5 choices but with a inactive dose of cocaine or a monetary reward. The order of days (active or inactive cocaine dosage) was random. These 2 testing days were completed during a 5-day in-hospital testing session under the progesterone condition and placebo condition. Progesterone and placebo conditions were randomized. Participants were asked to rate cocaine craving on a scale of 0-5 prior to administration of cocaine (active or inactive dose). Lower scores indicate less cocaine craving. | 4 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cocaine