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The Intermittent Oral Naltrexone Enhanced With an Ecological Momentary Intervention Study

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ClinicalTrials.gov Identifier: NCT04791969
Recruitment Status : Not yet recruiting
First Posted : March 10, 2021
Last Update Posted : March 10, 2021
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
This is a double-blind, placebo-controlled phase 2b trial in which 150 MSM who use meth will be randomly assigned (2:1) to receive 12 weeks of as-needed intermittent oral naltrexone 50 mg enhanced with an EMA-informed EMI platform, or receive as-needed placebo with EMA-informed EMI. The 12-week treatment period is consistent with other pharmacotherapy trials for substance use disorders. The proposed sample size is also consistent with other phase 2b trials for substance use treatment. Upon enrollment, participants will complete daily EMA assessments and weekly visits for behavioral surveys and sweat testing for meth metabolites, study drug dispensing and counseling for substance use. Safety laboratory assessments and vital signs will be completed monthly. Efficacy (Specific Aims 1-3) will be assessed upon trial completion as measured by proportion meth-positive sweat samples; PrEP and ART adherence by drug levels and viral load testing; and sexual risk behavior data accounting for PrEP use and viral suppression. Long-term treatment effects will be evaluated 3 months post-treatment.

Condition or disease Intervention/treatment Phase
Methamphetamine Use Disorder Drug: Naltrexone Hydrochloride Drug: Placebo Behavioral: Ecological Momentary Intervention Phase 2

Detailed Description:
Methamphetamine (meth) use is very common among men who have sex with men (MSM), particularly MSM living with HIV. Meth use among HIV-negative and HIV-positive MSM is up to 13 and 34 times more prevalent than in the general U.S. adult population, respectively. Meth use is independently associated with HIV-related sexual risk behaviors among MSM and can function as a barrier to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) adherence. Thus, effective interventions to reduce meth use may also function as an important HIV prevention and care intervention by reducing meth-related HIV risk behavior, and optimizing ART and PrEP adherence. MSM comprise two-thirds of the new infections in the United States. Despite this continued domestic HIV epidemic and the high prevalence of meth use among MSM, few interventions have proven efficacious for MSM who use meth. The investigators seek to address this gap by evaluating the efficacy of intermittent oral naltrexone enhanced with an ecological momentary intervention (ION+EMI) for meth use treatment. Naltrexone, a µ-opioid receptor antagonist, is a promising agent for MSM who use meth. Meth is rapidly metabolized to amphetamine in the bloodstream and daily naltrexone has shown efficacy in reducing amphetamine urine-positivity and relapse. Oral naltrexone is inexpensive and has few toxicities, but the standard daily regimen for naltrexone hampers compliance as patients frequently neglect to take the medication. Alternate regimen schedules have been proposed to increase efficacy and expand the population that may benefit from this pharmacologic agent. One alternative approach is the targeted administration of intermittent oral naltrexone (ION), whereby individuals are instructed to take the medication as needed in anticipation of substance use, after exposure to triggers of substance use, or during periods of craving. Administration of naltrexone prior to exposure to amphetamines significantly attenuated amphetamine craving in 4 trials. Additionally, emerging evidence suggests that ecological momentary interventions (EMI) that respond to in-the-moment contexts can lead to positive health behaviors, such as increasing medication dosing. EMI are particularly well-suited to enhancing as-needed dosing of naltrexone because anticipation of meth use and meth craving in a natural setting changes within a person from moment to moment, and the detection of these momentary fluctuations can support the delivery of just-in-time messages to encourage medication use to prevent participants from proceeding from craving to meth use. A pilot study led by our research team on ION found that meth-using MSM who use at least 1 day per week had significantly greater reductions in meth-using days when treated with as-needed naltrexone, compared to placebo. Moreover, naltrexone participants had greater reductions in serodiscordant receptive anal intercourse and serodiscordant condomless receptive anal intercourse, compared to placebo. In the pilot, participants reported taking study drug 64% of the days that they craved or anticipated meth use. Participants also completed ecological momentary assessments (EMA) with a 74% response rate, indicating that real-time assessments are feasible and acceptable. To build on the results of this study and 4 other naltrexone trials, the investigators propose to evaluate intermittent naltrexone to treat meth in a phase 2b efficacy trial supplemented by an EMA-informed EMI that responds to a participant's real-time craving levels or anticipated meth use to provide in-the-moment medication reminders when participants would most benefit from naltrexone. The investigators hypothesize that pairing ION with EMI will further amplify reductions in meth use by providing just-in-time reminders for naltrexone to optimize adherence, thereby interrupting the progression from craving to meth use.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 2:1 Naltrexone with EMI vs. Placebo with EMI
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-blind, placebo controlled 2b clinical trial
Primary Purpose: Treatment
Official Title: The ION+EMI Study: Intermittent Oral Naltrexone Enhanced With an Ecological Momentary Intervention for Methamphetamine-using MSM
Estimated Study Start Date : April 2021
Estimated Primary Completion Date : January 2026
Estimated Study Completion Date : March 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Naltrexone with ecological momentary intervention
Naltrexone Hydrochloride, 50 mg., intermittent with ecological momentary assessment (EMA)
Drug: Naltrexone Hydrochloride
Intermittent Oral Naltrexone, 50 mg
Other Name: ReVia

Behavioral: Ecological Momentary Intervention
Receive ecological momentary intervention if ecological momentary assessment reports meth craving, stress, not taking study drug, or antecedents detected for "high risk" meth use.
Other Name: EMI

Placebo Comparator: Placebo with ecological momentary intervention
Placebo, intermittent with ecological momentary assessment (EMA)
Drug: Placebo
Intermittent Oral Placebo

Behavioral: Ecological Momentary Intervention
Receive ecological momentary intervention if ecological momentary assessment reports meth craving, stress, not taking study drug, or antecedents detected for "high risk" meth use.
Other Name: EMI




Primary Outcome Measures :
  1. Mean Change in meth-positive sweat patches from baseline to week 12 between Intermittent Oral Naltrexone vs. placebo groups [ Time Frame: Every two weeks from enrollment to the end of treatment at 12 weeks ]
    As measured by the proportion of meth-positive sweat patch tests.


Secondary Outcome Measures :
  1. Mean change in sexual risk behaviors from baseline to week 12 between Intermittent Oral Naltrexone vs placebo groups. [ Time Frame: Every four weeks from enrollment to the end of treatment at 12 weeks ]
    As measured by reducing meth-associated sexual risk behaviors


Other Outcome Measures:
  1. Mean change in serum drug levels (PrEP) or ART suppression rates from baseline to week 12 between Intermittent Oral Naltrexone vs placebo groups. [ Time Frame: Every four weeks from enrollment to the end of treatment at 12 weeks ]
    As measured by serum drug-levels in HIV negative participants and viral suppression rates in HIV positive participants



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   cisgender male, men who have sex with men
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • cisgender male (male gender and sex assigned at birth)
  • age 18-70 years* (naltrexone's tolerability and safety has been demonstrated among older adults up to age 70)
  • self-reported condomless anal sex with men or missing Pre-Exposure Prophylaxis or antiretroviral therapy doses due to meth use in the prior three months while under the influence of meth
  • self-reported meth use at least weekly
  • interested in reducing meth use
  • no current acute illness requiring prolonged medical care
  • no chronic illness that is likely to progress clinically during trial
  • able and willing to provide informed consent and adhere to visit schedule
  • current CD4 count ≥ 200 cells/mm3; or CD4 count of 100-199 cells/mm3 and HIV viral load < 200 copies/mL (if living with HIV)
  • baseline complete blood count, total protein, albumin, glucose, alkaline phosphatase, creatinine, blood urea nitrogen test, and electrolytes without clinically significant abnormalities as determined by study clinician in conjunction with symptoms, physical exam, and medical history

Exclusion Criteria:

  • any psychiatric (e.g., depression with suicidal ideation) or medical condition that would preclude safe participation
  • known allergy or prior adverse reaction to naltrexone
  • current use of any opioids or a known medical condition which currently requires or may likely require opioid analgesics
  • opioid-positive urine test at screen/enrollment visits (naltrexone can induce opioid withdrawal)
  • moderate or severe liver disease (aspartate aminotransferase test, alanine aminotransferase test, or total bilirubin > 3 times upper limit of normal)
  • impaired renal function (creatinine clearance < 60 ml/min)
  • currently participating in another intervention research study with potential overlap
  • severe meth or alcohol use disorder as determined by structured clinical interview for DSM-5 criteria
  • any condition that, in the PI and/or study clinician's judgment interferes with safe participation or adherence to study procedures

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04791969


Contacts
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Contact: Glenn-Milo Santos, PhD, MPH 628-217-6231 glenn-milo.santos@ucsf.edu
Contact: Janet M Ikeda, MA 628-217-6204

Locations
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United States, California
San Francisco Department of Public Health
San Francisco, California, United States, 94102
Sponsors and Collaborators
University of California, San Francisco
National Institute on Drug Abuse (NIDA)
Investigators
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Principal Investigator: Glenn-Milo Santos, PhD, MPH University of California, San Francisco
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04791969    
Other Study ID Numbers: 20-32912
DA053171-01A1 ( Other Grant/Funding Number: National Institute on Drug Abuse )
First Posted: March 10, 2021    Key Record Dates
Last Update Posted: March 10, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of California, San Francisco:
Methamphetamine
meth
naltrexone
Additional relevant MeSH terms:
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Naltrexone
Alcohol Deterrents
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents