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| ID | Type | Description | Link |
|---|---|---|---|
| R21DA029914 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
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The investigators propose a placebo-controlled, randomized clinical trial that would enroll 50 postpartum women with a history of cocaine abuse or dependence to assess whether progesterone (100mgs twice daily) decreases postpartum cocaine use.
Specific Aim 1: To evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo.
Hypothesis 1: Compared to women who are randomized to placebo, those assigned to progesterone will use less cocaine as measured by urine toxicology results and self-reported days of use.
Specific aim 2: To obtain information about the safety and tolerability of progesterone treatment in the postpartum period.
Hypothesis 2: Side effects for progesterone will be similar to those of placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Matched placebo pills to be taken twice daily |
|
| Progesterone | Experimental | 100 mgs progesterone twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Progesterone | Drug | 100mgs progesterone twice daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Number of Days Per Week of Cocaine Use | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Measured by self-reported days of cocaine use per week via substance use calendar. | Weekly measurements, Baseline to 12 weeks |
| Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Measured by self-reported days of cocaine use per week during the trial period and during 3 month follow up using the substance use calendar | baseline, end of trial (week 12), 3-month post-trial follow-up |
| Proportion of Positive Urine Samples Per Week | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Urine tox tests obtained qualitative and quantitative data on cocaine metabolites and other substances. | weekly measurements, baseline to 12 weeks |
| Proportion of Positive Urine Samples Per Week | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Urine tox tests obtained qualitative and quantitative data on cocaine metabolites and other substances. | baseline, end of trial (week 12) and 3-month post-trial follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Comparison of Adverse Events Between Women in Placebo and Progesterone Group | To obtain information about the safety and tolerability of progesterone treatment in the postpartum period, women were queried at every visit about onset of adverse events, their seriousness, and their relatedness to study medication. Such data was monitored in SAETRS. | 12 weeks postpartum |
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Inclusion Criteria:
Exclusion Criteria:
Women will be ineligible for the trial if they:
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| Name | Affiliation | Role |
|---|---|---|
| Kimberly A Yonkers, MD | Yale University | Principal Investigator |
| Mehmet Sofuoglu, MD, PhD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale School of Medicine | New Haven | Connecticut | 06510 | United States |
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| Label | URL |
|---|---|
| Research site webpage | View source |
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Data request should be made to the PI
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75 women were scheduled for intake, but 24 did not complete intake interview and 1 was ineligible for randomisation because of a medical issue. The first 50 eligible women were randomly assigned.
On-site clinic screening assessments were performed in three obstetrics clinic associated with the Yale New Haven Hospital System in New Haven, CT, USA. Study referrals were accepted from the New Haven area. Both post-partum and pregnant women were screened. Screenings began in October of 2010 and finished in February of 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Matched placebo pills to be taken twice daily Placebo: Matched placebo pills to be taken twice daily |
| FG001 | Progesterone | 100 mgs progesterone twice daily Progesterone: 100mgs progesterone twice daily |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All 25 in each study group were included in intention-to-treat and safety analyses.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Matched placebo pills to be taken twice daily Placebo: Matched placebo pills to be taken twice daily |
| BG001 | Progesterone | 100 mgs progesterone twice daily Progesterone: 100mgs progesterone twice daily |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Number of Days Per Week of Cocaine Use | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Measured by self-reported days of cocaine use per week via substance use calendar. | intent-to-treat | Posted | Mean | Standard Deviation | number of days per week of cocaine use | Weekly measurements, Baseline to 12 weeks |
|
Adverse event data was collected over the entire study period, from the intake of the participants to their final 3-month follow-up.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Matched placebo pills to be taken twice daily Placebo: Matched placebo pills to be taken twice daily |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | General disorders |
|
Women seen only once per week leading to reliance on self-reports more than urine, results of which differed; post-partum women with cocaine use disorder have other issues affecting likelihood of cocaine use; missed visits may have biased results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kimberly A. Yonkers, M.D. | Yale University | 203-764-6621 | kimberly.yonkers@yale.edu |
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| ID | Term |
|---|---|
| D019970 | Cocaine-Related Disorders |
| ID | Term |
|---|---|
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D011374 | Progesterone |
| ID | Term |
|---|---|
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
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| Placebo | Other | Matched placebo pills to be taken twice daily |
|
| Cocaine Craving (Measured Weekly Using CCQ-Brief) | CCQ-Brief is a ten-item questionnaire developed from the 45-item CCQ. Each item is scored on a visual analogue scale ranging from 1-7, and items are averaged to yield a score from 1 to 7. Higher scores indicate stronger cocaine cravings. | baseline to 12 weeks |
| Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | EPDS scores were measured to detect depression as a possible adverse event and compare scores between the two groups. The scale consists of 10 items. Each item is scored from 0 to 3, and the 10 items are summed to calculate a total score with a possible range of 0 to 30 and higher scores indicating more severe depression. | baseline to 12 weeks |
| Salivary Progesterone Concentrations | A comparison of salivary progesterone concentrations across all samples for all timepoints | week 2, week 6, week 10, week 12 |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
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| Education | Number | participants |
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| Marital status | Number | participants |
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| Employment status | Number | participants |
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| Weeks post partum | Mean | Standard Deviation | weeks |
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| Lifetime cocaine use (years) | Mean | Standard Deviation | years |
|
| Age at first cocaine use (years) | Mean | Standard Deviation | years |
|
| Parity | Mean | Standard Deviation | births |
|
| EPDS score at intake | The Edinburgh Postnatal Depression scale measures depression and has 10 items with range of 0-30. Higher scores indicate more severe depression. | Mean | Standard Deviation | units on a scale |
|
| Baseline cocaine use (days per week) | Baseline cocaine use (days of use per week, averaged across 4 weeks prior to baseline, maximum value=7 days) | Mean | Standard Deviation | days |
|
| Not using cocaine at intake | Number | participants |
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| Methadone maintained | Number | participants |
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| Any lifetime major depressive episode | Number | participants |
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| Social phobia | Number | participants |
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| Obsessive compulsive disorder | Number | participants |
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| Generalized anxiety disorder | Number | participants |
|
| Post-traumatic stress disorder | Number | participants |
|
|
|
|
| Primary | Number of Days of Cocaine Use Between 12 Week Visits & the 3 Month Follow up | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Measured by self-reported days of cocaine use per week during the trial period and during 3 month follow up using the substance use calendar | intent-to-treat | Posted | Mean | 95% Confidence Interval | days of cocaine use between visits | baseline, end of trial (week 12), 3-month post-trial follow-up |
|
|
|
|
| Primary | Proportion of Positive Urine Samples Per Week | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Urine tox tests obtained qualitative and quantitative data on cocaine metabolites and other substances. | intent-to-treat | Posted | Mean | 95% Confidence Interval | proportion of positive urines per week | weekly measurements, baseline to 12 weeks |
|
|
|
|
| Primary | Proportion of Positive Urine Samples Per Week | Primary aim: to evaluate whether postpartum women with a history of cocaine abuse or dependence use less cocaine if they are randomized to progesterone than placebo. Urine tox tests obtained qualitative and quantitative data on cocaine metabolites and other substances. | intent-to-treat | Posted | Mean | 95% Confidence Interval | proportion of positive urines per week | baseline, end of trial (week 12) and 3-month post-trial follow-up |
|
|
|
|
| Secondary | Overall Comparison of Adverse Events Between Women in Placebo and Progesterone Group | To obtain information about the safety and tolerability of progesterone treatment in the postpartum period, women were queried at every visit about onset of adverse events, their seriousness, and their relatedness to study medication. Such data was monitored in SAETRS. | intent-to-treat | Posted | Number | adverse events | 12 weeks postpartum |
|
|
|
|
| Secondary | Cocaine Craving (Measured Weekly Using CCQ-Brief) | CCQ-Brief is a ten-item questionnaire developed from the 45-item CCQ. Each item is scored on a visual analogue scale ranging from 1-7, and items are averaged to yield a score from 1 to 7. Higher scores indicate stronger cocaine cravings. | intent-to-treat | Posted | Mean | 95% Confidence Interval | units on a scale | baseline to 12 weeks |
|
|
|
|
| Secondary | Depression (Measured Weekly Using Edinburgh Postnatal Depression Scale (EPDS)) | EPDS scores were measured to detect depression as a possible adverse event and compare scores between the two groups. The scale consists of 10 items. Each item is scored from 0 to 3, and the 10 items are summed to calculate a total score with a possible range of 0 to 30 and higher scores indicating more severe depression. | intent-to-treat | Posted | Mean | Standard Error | units on a scale | baseline to 12 weeks |
|
|
|
| Secondary | Salivary Progesterone Concentrations | A comparison of salivary progesterone concentrations across all samples for all timepoints | intent-to-treat | Posted | Mean | Standard Error | pg/ml of salivary progesterone | week 2, week 6, week 10, week 12 |
|
|
|
| Post-Hoc | Relapse to Cocaine Use During Treatment Period | Post-hoc sensitivity test to compare hazard of relapse to cocaine use between two treatment groups among participants (n=41) who did not report using cocaine at intake. | intent-to-treat | Posted | Number | participants who relapsed to cocaine use | baseline to 12 weeks |
|
|
|
|
| Post-Hoc | Relapse to Cocaine Use During Treatment Period or 3 Months Post Treatment | Post-hoc sensitivity test to compare hazard of relapse to cocaine use between two treatment groups among participants (n=41) who did not report using cocaine at intake. | intent-to-treat | Posted | Number | participants who relapsed to cocaine use | baseline to 3 months post 12-week trial period |
|
|
|
|
| 0 |
| 25 |
| 11 |
| 25 |
| EG001 | Progesterone | 100 mgs progesterone twice daily Progesterone: 100mgs progesterone twice daily | 0 | 25 | 15 | 25 |
| Sedation | General disorders |
|
| Dizziness | General disorders |
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| Dry mouth | General disorders |
|
| Nausea | General disorders |
|
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| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D003339 | Corpus Luteum Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045167 | Progesterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| 3-Month Post-Trial Follow-Up |
|
| Superiority or Other |
| Negative binomial distribution, log link, and first-order autoregressive covariance structure | Generalized Estimating Equation | 0.038 | Risk Ratio (RR) | 16.65 | 2-Sided | 95 | 1.18 | 235.52 | Estimated value is RR for treatment*time interaction term for placebo at week 12. Time was treated as a 3-level categorical variable; week 0 (ref), week 12 and 3-month post-trial follow-up. Treatment variable reference group was progesterone. | Superiority or Other |
| Week 2 |
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| Week 11 |
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| Week 12 |
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| 3 month post-trial follow-up |
|
| Generalized Estimating Equation | Negative binomial distribution, log link, and first-order autoregressive covariance structure | 0.84 | Risk Ratio (RR) | 1.18 | 2-Sided | 95 | 0.24 | 5.84 | Estimated value is RR for treatment*time interaction for placebo at week 12. Time was treated as a 3-level categorical variable; week 0 (ref), week 12 & 3-month post-trial follow-up. Treatment variable reference group was progesterone. | Superiority or Other |
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