Naltrexone and bupropion for the treatment of methamphetamine use disorder
An open-label safety and feasibility pilot trial of oral naltrexone-bupropion combination pharmacotherapy for methamphetamine use disorder
St Vincent's Hospital Sydney
20 participants
Oct 2, 2023
Interventional
Conditions
Summary
This study aims to determine the safety and feasibility of a combination of orally administered medications (naltrexone and bupropion) for people with methamphetamine use disorder in an outpatient drug and alcohol treatment setting. There are currently no approved medications in Australia to help people manage, reduce, or stop their methamphetamine use. It is hoped that this study will help find out if taking naltrexone and bupropion together everyday over a 12-week period is a safe and feasible treatment approach for methamphetamine use disorder .
Eligibility
Inclusion Criteria11
- Greater than or equal to 18 years of age
- Able to provide informed consent
- Interested in managing, reducing, or stopping methamphetamine use
- Meet DSM-5-TR diagnostic criteria for Stimulant Use Disorder – Amphetamine-Type Substance assessed at enrolment
- Self-report methamphetamine use at least 14 days out of the previous 28 at baseline using the Timeline Follow-back (TLFB) method, assessed within 24 hours of first scheduled study dose
- Opioid free for at least 7 concurrent days (self-report), assessed within 24 hours of first scheduled study dose
- Provide a urine sample positive for methamphetamine and negative for opioids within 24 hours of first scheduled study dose
- If person of childbearing potential, willingness to undergo a pregnancy test within 24 hours of first scheduled study dose and avoid pregnancy during the entire study duration
- Meet subjective and objective measures of being opioid-free prior to naltrexone induction, according to the determination of the PI at enrolment
- Willing and able to comply with all study requirements, including ability to store study medications securely
- Agree to use a smartphone to self-report daily adherence to the study medication
Exclusion Criteria21
- Currently pregnant or breastfeeding, or planning on becoming pregnant during the course of the study
- Presence of any psychiatric or physical comorbidity that would interfere with study participation as assessed by the PI
- Presence of any factors that increase risk of seizure, including a history of epilepsy, seizure disorder, or head trauma with associated loss of consciousness that required hospitalisation, current anorexia nervosa or bulimia, or any other conditions that increase seizure risk in the opinion of the study’s medical monitor
- Coexisting dependence on alcohol, benzodiazepines, GHB, or opiates, or undergoing treatment for any other substance use disorder
- Expected need for opioid-containing medications at any point during the study (e.g. planned surgery)
- Current use of medications associated with serotonin syndrome, including selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs)
- Liver function tests (LFT) indicating elevated levels as follows: AST/ALT results > 5 times ULN, total bilirubin > 2 times ULN, or platelets below 75 x 103/µL
- Contraindications for naltrexone hydrochloride as per the Australian Product Information Sheet:
- o Patients receiving opioid analgesics.
- o Patients currently dependent on opioids since an acute withdrawal syndrome may ensue.
- o Patients in acute opioid withdrawal.
- o Any individual with a history of sensitivity to naltrexone or any other components of this product. It is not known if there is any cross-sensitivity with naloxone or the phenanthrene containing opioids.
- o Any individual with acute hepatitis or liver failure. Naltrexone GH should not be given to patients with acute hepatitis or liver failure.
- Contraindications for bupropion hydrochloride sustained release tablets as per the Australian Product Information Sheet:
- o Patients with hypersensitivity to bupropion or any of the other components of the preparation.
- o Patients with a current seizure disorder or any history of seizures.
- o Patients with a known central nervous system (CNS) tumour.
- o Patients undergoing abrupt withdrawal from alcohol or benzodiazepines.
- o Patients currently being treated with any other preparation containing bupropion as the incidence of seizures is dose dependent.
- o Patients with a current or previous diagnosis of bulimia or anorexia nervosa.
- o Concomitant use of bupropion hydrochloride and monoamine oxidase inhibitors (MAOIs). At least 14 days should elapse between discontinuation of MAOIs and initiation of treatment with bupropion hydrochloride tablets.
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Interventions
Commercially available oral tablets containing naltrexone hydrochloride 8 mg and bupropion hydrochloride 90 mg (branded Contrave 8/90). Week 1 – 12: Medication Period and Primary Endpoint (days 1 – 84) Participants will receive an increasing dose regimen as follows: • Day 1: 1 tablet morning (total 1 tablet per day) • Day 2: 1 tablet morning & 1 tablet evening (total 2 tablets per day) • Day 3: 2 tablets morning & 1 tablet evening (total 3 tablets per day) • Day 4: 2 tablets morning & 2 tablets evening (total 4 tablets per day) • Day 5: 3 tablets morning & 2 tablets evening (total 5 tablets per day) From day 5 onwards the dose will remain at 5 tablets daily (3 morning, 2 evening) for the remainder of the 12 week medication period (to day 84 inclusive). In Week 13 (day 85 to 88), the dose will be gradually decreased then ceased, as follows: Week 13: Taper-down Period (days 85 – 88) • Day 85: 2 tablets morning & 2 tablets evening (4 tablets per day) • Day 86: 2 tablets morning & 1 tablets evening (3 tablets per day) • Day 87: 1 tablet morning & 1 tablet evening (2 tablets per day) • Day 88: 1 tablet morning FINAL DOSE (1 tablet per day) Adherence will be assessed by two means: • Self-reported medication adherence (via brief smartphone survey) sent daily • Simplified Medication Adherence Questionnaire (SMAQ) administered at each weekly clinic visit
Locations(1)
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ACTRN12623000866606