Official Title: “Progesterone Treatment for Cocaine-Dependent Women: A Pilot Study”

The purpose of this pilot treatment trial is to evaluate the efficacy of oral micronized PROG in cocaine-dependent women. Since we have shown (Evans & Foltin, 2006) that oral micronized PROG attenuates the positive subjective effects of smoked cocaine in females, but not in males, and we have preliminary data indicating that oral micronized PROG also reduces smoked cocaine self-administration in the laboratory, PROG appears to be an ideal potential candidate medication to evaluate in cocaine-dependent women. Prior to randomization to treatment, women will reside inpatient for one week to ensure cocaine abstinence since one of the primary outcome measures will be time to cocaine relapse.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: February 2012

Primary Aims: The primary aims will be directed at treatment efficacy. Relatively unique to cocaine treatment trials, one of the principal outcome measures will be time to cocaine relapse. We hypothesize that maintenance on PROG will increase the time to cocaine relapse compared to maintenance on placebo (PBO). Another cocaine-related efficacy endpoint will be the proportion of patients who achieve at least 2 consecutive weeks of cocaine abstinence (based on urine toxicology results) during the double-blind treatment phase. Lastly, the proportion of cocaine-negative urines collected throughout the treatment trial will be measured. We hypothesize that women in the PROG group will show a greater reduction in cocaine use compared to those in the PBO group.

Secondary Aims: 1) Determine if response to laboratory stressors will predict treatment outcome. We hypothesize that those women with the greatest stress response will do worse in treatment and that maintenance on PROG will reduce stress/anxiety and thereby improve treatment outcome. 2) Determine if treatment retention is better in the PROG group compared to the PBO group and determine if maintenance on PROG improves overall functioning compared to maintenance on PBO based on the Clinical Global Inventory (CGI). We hypothesize that women in the PROG group will have better treatment retention and improvement in CGI scores compared to women in the PBO group.

Tertiary Aims: To conduct exploratory analyses to determine whether 1) trauma history is related to treatment outcomes and 2) improvements in treatment outcome measures are related to decreases in HIV high-risk behaviors.

Intervention(s) in this Clinical Trial

• Drug: Oral micronized progesterone
  • Oral micronized progesterone (up to 400 mg/day), suspended in olive oil
• Drug: Placebo
  • matched placebo

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 2
  • matched placebo
• Experimental: 1
  • Oral micronized progesterone (up to 400 mg/day)

Primary Measures

• Urine toxicology results
  • Time Frame: 3x/week
    Safety Issue?: No

Secondary Measures

• self reported cocaine use
  • Time Frame: daily
    Safety Issue?: No

Inclusion Criteria:

• 1. Women between the ages of 18-45 who meet criteria for current cocaine dependence (DSM-IV-TR). Volunteers may meet criteria for abuse or dependence on nicotine, marijuana or alcohol, as long as the dependence is secondary to cocaine dependence and does not require any medical intervention (see additional exclusions for alcohol dependence below).
• 2. Use cocaine at least four days in the past month, with at least weekly cocaine use, and smoked cocaine is the primary route of use.
• 3. Women with regular menstrual cycles (24-45 days) who are not pregnant, based on the results of a blood pregnancy test drawn at the time of screening. They must agree to use a barrier method of contraception with proven efficacy and agree not to become pregnant during the study. To confirm this, urine pregnancy tests will be conducted weekly.
• 4. Women must be capable of giving informed consent and capable of complying with study procedures.

Exclusion Criteria:

• 1. Meets DSM-IV-TR criteria for bipolar disorder, Schizophrenia, or any psychotic disorder other than transient psychosis due to drug abuse.
• 2. Individuals with any current Axis I psychiatric disorder as defined by DSM-IV-TR supported by the SCID-I/P that in the investigator's judgment are unstable or would be disrupted by study medication. Disorders that are stable on psychotherapy or pharmacotherapy will not be exclusionary. Individuals will be permitted to take prescribed zolpidem and zaleplon if there is no evidence of dependence on these substances.
• 3. Individuals with current major depressive disorder.
• 4. Individuals physiologically dependent on any other drugs (excluding nicotine or cannabis) that require medical intervention will be excluded and referred for treatment. Individuals with severe alcohol dependence , even without physiological dependence, or with any known alcohol-related diseases will also be excluded.
• 5. Females who have any of the following medical contraindications: undiagnosed abnormal genital bleeding, known or suspected history of breast or genital cancer, active deep vein thrombosis, pulmonary embolism, or history of these conditions, active or recent (within last year) arterial thromboembolic diseases (e.g., stroke, myocardial infarction), liver dysfunction.
• 6. Females who are cognitively impaired or have a chronic organic mental disorder.
• 7. Individuals with current suicidal risk.
• 8. Individuals with coronary vascular disease as indicated by history or suspected by abnormal ECG or history of cardiac symptoms.
• 9. Unstable physical disorders which might make participation hazardous such as uncontrolled hypertension (SBP > 150, DBP> 90, or HR > 100 when sitting quietly), acute hepatitis (patients with chronic mildly elevated transaminases < 3x upper limit of normal are acceptable), or uncontrolled diabetes.
• 10. Individuals with a history of seizures.
• 11. Women who are pregnant or nursing.
• 12. Individuals who are legally mandated (e.g., to avoid incarceration, monetary or other penalties, etc.) to participate in substance abuse treatment program.
• 13. Females with a known or suspected hypersensitivity to oral micronized progesterone.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute on Drug Abuse (NIDA)

Overall Clinical Trial Officials and Contacts

Suzette Evans, PhD Principal Investigator Columbia University  

Overall Contact: Cassie Glanton, MA 212- 923-3031 glanton@pi.cpmc.columbia.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00632099

Study ID Number: RO1DA022218

ClinicalTrials.gov Identifier: NCT00632099

Health Authority: United States: Federal Government