Progesterone for the Treatment of Cocaine Dependence - 1

Interactions Between Progesterone and Cocaine in Women

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.

Study Overview

• Status: Completed
• Conditions: Cocaine-Related Disorders; Cocaine Abuse
• Intervention / Treatment: Other: Placebo; Drug: Progesterone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 46 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo twice daily	Other: Placebo; placebo
ACTIVE_COMPARATOR: Progesterone; 200mg progesterone twice daily	Drug: Progesterone; 200mg progesterone twice daily; Other Names: prometrium

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Sheila M. Specker, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start: July 1, 2002
• Primary Completion (ACTUAL): April 1, 2008
• Study Completion (ACTUAL): June 30, 2008

Study Registration Dates

• First Submitted: September 16, 2005
• First Submitted That Met QC Criteria: September 16, 2005
• First Posted (ESTIMATE): September 22, 2005

Study Record Updates

• Last Update Posted (ACTUAL): October 8, 2020
• Last Update Submitted That Met QC Criteria: September 11, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Cocaine
• 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: 0205M23681; DPMC (Other Identifier: NIDA); R01DA014573 (NIH)