Cocaine Abuse, Cocaine-Related Disorders
Conditions
Keywords
Cocaine
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.
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.
Interventions
DRUGProgesterone
200mg progesterone twice daily
OTHERPlacebo
placebo
Sponsors
National Institute on Drug Abuse (NIDA)
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 46 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Cross-over design; all participants who completed the first of two inpatient study visits are pooled and reported here | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period Between Visit 1 and 2 | Lost to Follow-up | 4 | 3 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants |
| Age, Continuous | 40 Years STANDARD_DEVIATION 5.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 0 / 38 |
| other Total, other adverse events | 14 / 38 | 0 / 38 |
| serious Total, serious adverse events | 1 / 38 | 0 / 38 |
Outcome results
Primary
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.
Time frame: 4 days
Population: Only participants who completed both 4-day in-hospital testing visits are included in outcome measure reporting.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Progesterone | Decision to Self-Administer Cocaine | Active Cocaine Dose | 66 percent of available doses | Standard Error 3.5 |
| Progesterone | Decision to Self-Administer Cocaine | Inactive Cocaine Dose | 32 percent of available doses | Standard Error 3.5 |
| Placebo | Decision to Self-Administer Cocaine | Active Cocaine Dose | 66 percent of available doses | Standard Error 3.3 |
| Placebo | Decision to Self-Administer Cocaine | Inactive Cocaine Dose | 32 percent of available doses | Standard Error 3.3 |
Secondary
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.
Time frame: 4 days
Population: Only participants who completed both 4-day in-hospital testing visits are included in outcome measure reporting.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Progesterone | Cocaine Craving | Inactive Cocaine Dose | 2.06 score on a scale | Standard Error 0.16 |
| Progesterone | Cocaine Craving | Active Cocaine Dose | 3.99 score on a scale | Standard Error 0.17 |
| Placebo | Cocaine Craving | Active Cocaine Dose | 4.02 score on a scale | Standard Error 0.16 |
| Placebo | Cocaine Craving | Inactive Cocaine Dose | 1.38 score on a scale | Standard Error 0.17 |
Secondary
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.
Time frame: 4 days
Population: Only participants who completed both 4-day in-hospital testing visits are included in outcome measure reporting.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Progesterone | Diastolic Blood Pressure | Active Cocaine Dose | 77.6 mmHG | Standard Deviation 12.6 |
| Progesterone | Diastolic Blood Pressure | Inactive Cocaine Dose | 71.3 mmHG | Standard Deviation 8.8 |
| Placebo | Diastolic Blood Pressure | Active Cocaine Dose | 78.6 mmHG | Standard Deviation 10.7 |
| Placebo | Diastolic Blood Pressure | Inactive Cocaine Dose | 72.2 mmHG | Standard Deviation 10.1 |
Secondary
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.
Time frame: 4 days
Population: Only participants who completed both 4-day in-hospital testing visits are included in outcome measure reporting.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Progesterone | Heart Rate | Inactive Cocaine Dose | 77.6 beats per minute | Standard Deviation 13 |
| Progesterone | Heart Rate | Active Cocaine Dose | 87.9 beats per minute | Standard Deviation 16 |
| Placebo | Heart Rate | Inactive Cocaine Dose | 74.6 beats per minute | Standard Deviation 12.1 |
| Placebo | Heart Rate | Active Cocaine Dose | 87.2 beats per minute | Standard Deviation 16.3 |
Secondary
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.
Time frame: 4 days
Population: Only participants who completed both 4-day in-hospital testing visits are included in outcome measure reporting.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Progesterone | Systolic Blood Pressure | Active Cocaine Dose | 129.9 mmHG | Standard Deviation 19.8 |
| Progesterone | Systolic Blood Pressure | Inactive Cocaine Dose | 117.4 mmHG | Standard Deviation 16.6 |
| Placebo | Systolic Blood Pressure | Inactive Cocaine Dose | 120.2 mmHG | Standard Deviation 17.6 |
| Placebo | Systolic Blood Pressure | Active Cocaine Dose | 131.8 mmHG | Standard Deviation 18.5 |