Methamphetamine-dependence, Postpartum Abstinence
Conditions
Keywords
Pregnancy, Postpartum
Brief summary
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
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
Interventions
DRUGProgesterone
Randomized to 400 mg (200 mg twice daily) oral micronized progesterone daily
DRUGPlacebo
Randomized to placebo twice daily
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double blind, placebo controlled
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful Recruitment and Randomization of 40 Postpartum Women Into the PROMPT Study | 15 months after study initiation | Recruit and enroll 40 eligible women (postpartum individuals with MUD) in a 15 month period from time of study initiation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Severe Medication Side Effects | Baseline and 12 weeks | Number of enolled participants with Severe Medication Side Effects |
| Assess Depression and Suicidality Status in Enrolled Participants | Baseline and 12 weeks | A lower score on the Edinburgh Postpartum Depression Scale (EPDS) scale indicates a better outcome. The Edinburgh Postnatal Depression Scale (EPDS) is a 10-item screening tool (maximum score 30) used to identify perinatal depression, where scores 0-9 indicate minimal depression, scores of 10 or higher typically indicate possible depression, and scores of 13 or greater strongly suggest a depressive illness. |
| Assess Anxiety Status in Enrolled Participants | Baseline and 12 weeks | Assess anxiety status in enrolled participants using validated surveys/ GAD-7 The GAD-7 (Generalized Anxiety Disorder-7) is a 7-item, self-reported questionnaire used to measure anxiety severity over the past two weeks. Scores range from 0 to 21, categorized as mild (0-4), moderate (5-9), moderately severe (10-14), and severe (15-21) anxiety. A score of 10 or higher is the typical cutoff for identifying clinical anxiety |
| Difference in Tobacco Use From Baseline | Baseline and 12 weeks | Secondarily we assessed the association between the exposures of doses of progesterone administered and tobacco use. |
| Assess Return to Methamphetamine Use (MU) in Enrolled Participants | Baseline and 12 weeks | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMarcela Smid, MD
University of Utha
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants |
| Age, Continuous | 31.9 years STANDARD_DEVIATION 4.9 |
| Race/Ethnicity, Customized More than one Race | 0 participants |
| Race/Ethnicity, Customized Race : Asian | 1 participants |
| Race/Ethnicity, Customized Race : Black | 3 participants |
| Race/Ethnicity, Customized Race : Native Hawaiin/ PI | 1 participants |
| Race/Ethnicity, Customized Race : White | 16 participants |
| Region of Enrollment United States | 34 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 16 |
| other Total, other adverse events | 14 / 18 | 13 / 16 |
| serious Total, serious adverse events | 3 / 18 | 1 / 16 |
Outcome results
None listed