Progesterone for the Treatment of Cocaine Dependence - 1

• Sponsor: University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT00218257
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 96
• Location: 1
• Arms: 2
• Duration (Months): 72
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Abuse; Cocaine-Related Disorders	Drug: Progesterone; Other: Placebo	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention 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.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 (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Interactions Between Progesterone and Cocaine in Women
• Study Start Date: Jul 1, 2002
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Jun 30, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Progesterone 200mg progesterone twice daily	Drug: Progesterone; 200mg progesterone twice daily; Other Names: prometrium
Placebo Comparator: Placebo Placebo twice daily	Other: Placebo; placebo

Outcome Measures

Primary Outcome Measures

1. Decision to Self-Administer Cocaine [4 days]

   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.

Secondary Outcome Measures

1. Heart Rate [4 days]

   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.

2. Systolic Blood Pressure [4 days]

   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.

3. Diastolic Blood Pressure [4 days]

   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. Cocaine Craving [4 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 46 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• University of Minnesota
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Sheila M. Specker, MD, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Minnesota
• ClinicalTrials.gov Identifier: NCT00218257
• Other Study ID Numbers: 0205M23681; R01DA014573; DPMC
• First Posted: Sep 22, 2005
• Last Update Posted: Oct 8, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by University of Minnesota: Cocaine
• Additional relevant MeSH terms: Cocaine-Related Disorders; Progesterone

Study Results

Participant Flow

Pre-assignment Detail	96 participants were consented. 45 participants began the first in-hospital study visit. The remaining 41 participants were lost to follow-up or chose not to participant after consenting. 45 participants completed the first 4-day inpatient study visit. 38 participants began and completed the second inpatient study visit.

Arm/Group Title	Progesterone, Then Placebo	Placebo, Then Progesterone
Arm/Group Description
Period Title: Intervention 1
STARTED	23	22
COMPLETED	23	22
NOT COMPLETED	0	0
Period Title: Intervention 1
STARTED	23	22
COMPLETED	19	19
NOT COMPLETED	4	3
Period Title: Intervention 1
STARTED	19	19
COMPLETED	19	19
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Cross-over design; all participants who completed the first of two inpatient study visits are pooled and reported here
Overall Participants	45
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	45 100%
>=65 years	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40 (5.4)
Sex: Female, Male (Count of Participants)
Female	22 48.9%
Male	23 51.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.2%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	25 55.6%
White	12 26.7%
More than one race	0 0%
Unknown or Not Reported	7 15.6%
Region of Enrollment (participants) [Number]
United States	45 100%

Outcome Measures

1. Primary Outcome

Title	Decision to Self-Administer Cocaine
Description	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.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

Only participants who completed both 4-day in-hospital testing visits are included in outcome measure reporting.

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Progesterone (200mg, twice daily)	Placebo (given twice daily)
Measure Participants	38	38
Active Cocaine Dose	66 (3.5)	66 (3.3)
Inactive Cocaine Dose	32 (3.5)	32 (3.3)

2. Secondary Outcome

Title	Heart Rate
Description	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.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

Only participants who completed both 4-day in-hospital testing visits are included in outcome measure reporting.

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Progesterone (200mg, given twice daily)	Placebo (given twice daily)
Measure Participants	38	38
Active Cocaine Dose	87.9 (16.0)	87.2 (16.3)
Inactive Cocaine Dose	77.6 (13.0)	74.6 (12.1)

3. Secondary Outcome

Title	Systolic Blood Pressure
Description	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.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

Only participants who completed both 4-day in-hospital testing visits are included in outcome measure reporting.

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Progesterone (200mg twice daily)	Placebo (given twice daily)
Measure Participants	38	38
Active Cocaine Dose	129.9 (19.8)	131.8 (18.5)
Inactive Cocaine Dose	117.4 (16.6)	120.2 (17.6)

4. Secondary Outcome

Title	Diastolic Blood Pressure
Description	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.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

Only participants who completed both 4-day in-hospital testing visits are included in outcome measure reporting.

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Progesterone (200mg given twice daily)	Placebo (given twice daily)
Measure Participants	38	38
Active Cocaine Dose	77.6 (12.6)	78.6 (10.7)
Inactive Cocaine Dose	71.3 (8.8)	72.2 (10.1)

5. Secondary Outcome

Title	Cocaine Craving
Description	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.
Time Frame	4 days

Outcome Measure Data

Analysis Population Description

Only participants who completed both 4-day in-hospital testing visits are included in outcome measure reporting.

Arm/Group Title	Progesterone	Placebo
Arm/Group Description	Progesterone (200mg twice daily)	Placebo (given twice daily)
Measure Participants	38	38
Active Cocaine Dose	3.99 (.17)	4.02 (.16)
Inactive Cocaine Dose	2.06 (.16)	1.38 (.17)

Adverse Events

Time Frame	2 months
Arm/Group Title	Progesterone		Placebo
Arm/Group Description	Progesterone (200mg given twice daily)		Placebo (given twice daily)
All Cause Mortality
	Progesterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/38 (0%)
Serious Adverse Events
	Progesterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/38 (2.6%)		0/38 (0%)
Nervous system disorders
Seizure	1/38 (2.6%)	1	0/38 (0%)	0
Other (Not Including Serious) Adverse Events
	Progesterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/38 (36.8%)		0/38 (0%)
Gastrointestinal disorders
GI Upset	7/38 (18.4%)	7	0/38 (0%)	0
Nervous system disorders
Headache	7/38 (18.4%)		0/38 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.