PRevention Of Methamphetamine Use Among Postpartum Women Trial (PROMPT)

Study Overview
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Brief Summary
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The PRevention Of Methamphetamine Use among Postpartum Women Trial (PROMPT) is randomized controlled trial of postpartum individuals with methamphetamine use disorder to 12 weeks of 200 mg oral micronized progesterone twice daily or placebo. The aims of this study are to assess the feasibility, safety and preliminary efficacy of micronized progesterone for the prevention of return to methamphetamine use. A secondary aim is to assess participant's salivary levels of allopregnanolone with methamphetamine cravings. This study has the potential to provide effective interventions to prevent methamphetamine use among postpartum women.

Detailed Description
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While substantial attention and resources have been directed at the opioid epidemic in the US, another deadly drug epidemic - methamphetamine use (MU) - has been evolving. While most pregnant women achieve abstinence by late pregnancy, the postpartum period is a particularly vulnerable time. Postpartum return to use is high and potentially deadly. Data from the Utah Maternal Mortality Review Committee indicate that from 2005-2016 (n=176), MU contributed to one out of every five deaths of pregnant and postpartum women; 85% of these deaths occurred in the postpartum period and, 70% of methamphetamine-related deaths also involved opioids. While medications for OUD reduce return to opioid use among postpartum women, similar interventions to reduce return to MU are lacking. In developing novel interventions to address MU in this vulnerable population, it is critical to consider important hormonal changes that mediate drug cravings and place postpartum women at particular risk of return to MU. Among women, higher systemic levels of progesterone and its active metabolite allopregnanolone appear to attenuate drug craving, urges, and return to use. Postpartum women may be particularly sensitive to increased craving and urges given the precipitous post-delivery drop in endogenous progesterone and allopregnanolone levels. Supplementation of exogenous progesterone is a novel therapy that has shown promising results in decreasing return to use among women using cocaine, tobacco, and benzodiazepines. Among postpartum women who used cocaine in pregnancy, micronized progesterone (which metabolizes to allopregnanolone) was associated with a reduction in cocaine use in the first 12 weeks postpartum in a randomized, placebo-controlled trial. The investigator's long-term goal is to advance the understanding of how pregnant and postpartum women's unique physiology impacts the trajectory of MUD and to apply this knowledge to developing novel interventions aimed at reducing MU in this population. The objectives of the PROMPT study is to determine: 1) the effect of micronized progesterone on return to MU among postpartum women with MUD, and, 2) determine the association between allopregnanolone levels and methamphetamine craving in this population. The central hypothesis is that micronized progesterone is a feasible, safe, and effective intervention that reduces the risk of return to MU among postpartum women with methamphetamine use disorder

Official Title
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PRevention Of Methamphetamine Use Among Postpartum Women Trial (PROMPT)

Conditions
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Methamphetamine-dependence, Postpartum Abstinence

Intervention / Treatment
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* Drug: Progesterone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meeting criteria for substance use disorder of methamphetamine in the six months prior to conception or during pregnancy No active methamphetamine use at time of enrollment or within past 4 weeks prior to enrollment by self-report or urine toxicology. If diagnosis of active opioid use disorder (OUD) and no use at time of enrollment or within past 4 weeks prior to enrollment by self-report or urine toxicology and on stable dose of medication for OUD (methadone, buprenorphine, naltrexone) for two weeks prior to enrollment in order to allow for postpartum dose adjustments. Intrauterine device or barrier method for contraception during the study period End of pregnancy within past 12 weeks Residing within 100 miles of study site Stable on allowable psychiatric medications including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and mood stabilizers for four weeks prior to enrollment Exclusion Criteria: Major medical illness in which progesterone may be contraindicated (significant liver disease, history of thrombophlebitis, stroke, heart disease, suspected or known malignancy, deep vein thrombosis, pulmonary embolus, clotting or bleeding disorders) Any of the following laboratory abnormalities (within 2 weeks of screening and enrollment) Active hepatic dysfunction Anemia defined as hemoglobin less than 8 g/dL indicating anemia Renal impairment defined as creatinine greater than 2.0 mg/dL Hypothyroidism defined as TSH greater than 5 mIU/L Abnormal vital signs at baseline visit Allergy to micronized progesterone or ingredients in placebo including peanut oil, gelatin or cellulose Self-reported progestin-containing oral or depot containing contraceptives intolerance. Do not speak English or Spanish Taking potent inhibitors of CY P450 3A4 including clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil and goldenseal. Severe depressive symptoms Active suicidality Current or past history of psychosis, suicidal attempts or psychiatric hospitalizations Current or pending incarceration Active alcohol use disorder within past six months Use of the following concomitant drugs, supplements and over-the-counter medications in the two week prior to enrollment: stimulants, barbiturates, benzodiazepines, non-benzodiazepine hypnotics, orexin antagonists, first generation anti-histamine, herbal sedatives, methaqualone and analogues, skeletal muscle relaxants, opioids (other than methadone or buprenorphine), anti-psychotic medications, certain anti-depressants or other medication with significant sedative properties as evaluated by the PI and/or study clinician. Progestin containing medications including oral hormonal contraceptive methods

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Progesterone Arm<br>Randomized to receive progesterone | Drug: Progesterone<br>* Randomized to 400 mg (200 mg twice daily) oral micronized progesterone daily<br>|
| Placebo Comparator: Placebo Arm<br>Randomized to receive placebo | Drug: Placebo<br>* Randomized to placebo twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful recruitment and randomization of 40 postpartum women into the PROMPT study | Recruit and enroll 40 eligible women in a 15 month period from time of study initiation. | 15 months after study initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess medication side effects through review of the GASE in enrolled participants | Investigators will track medication side effects over the study period by reviewing participant responses to the GASE (Generic Assessment of Side Effects). Benchmark is fewer than 20% positivity, based on GASE. | 12 weeks | 
| Assess depression and suicidality status in enrolled participants | Depression and suicidality will be assessed through review of Edinburgh Postnatal Depression Scale (EPDS) at weekly study visits. Edinburg postnatal depression scale min 0 max 30; increase in score indicates higher depression with any response above 0 on question 10 indicates potential suicidality. Benchmark is fewer than 5% of participants with have a greater than 30% increase in EPDS score that cannot be attributed to anything else. | 12 weeks | 
| Assess anxiety status in enrolled participants | Anxiety will be assessed through review of the General Anxiety Disorder-7 (GAD-7) screening tool at weekly study visits. Generalized anxiety disorder 7 (GAD7) scale has minimum of zero and a maximum of 21. Benchmark is fewer than 5% of participants with have a greater than 30% increase in GAD-7 score that cannot be attributed to anything else. | 12 weeks | 
| Assess breastfeeding difficulty in enrolled participants | Breastfeeding difficulties will be assessed through review of the Bristol Breastfeeding Assessment Form at weekly study visits. Benchmark is subjects expressing difficulty less than 30%, based on Bristol Breastfeeding Assessment Form. | 12 weeks | 
| Assess return to methamphetamine use (MU) in enrolled participants | Assess the efficacy of micronized progesterone to decrease return to methamphetamine use (MU) among postpartum women with methamphetamine use disorder. Return to use will be defined as either self-reported MU or positive urine toxicology result. Results will be compared between placebo and active ingredient groups. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy, Postpartum