Anti-retroviral Therapy, Medications for Opioid Use Disorder, Opioids and HIV Infection - Study 1

NCT04480554 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: R01DA048728
• Study Type: interventional
• Target: 225
• Locations: 2 countries
• Sites: 2

Brief Summary

HIV infection, as well as exposure to opioids (including heroin), are associated with systemic immune activation including increased microbial translocation from the gut. The overall objective of this study is to define the impact of long-term mu-opiate receptor stimulation or blockage with medication for opiate use disorder (i.e, methadone, buprenorphine/naloxone, or extended-release naltrexone) on the kinetics and extent of immune reconstitution on HIV-1 infected people who inject opiate and initiating antiretroviral therapy.

Conditions

Opioid-use Disorder; HIV-1-infection; Immune Activation; Inflammation; Methadone; Buprenorphine; Naltrexone; Antiretroviral Treatment

Keywords

Opioid use disorder; HIV; Medication for Opioid Use Disorder; Antiretroviral therapy; Immune activation

Outcome Measures

Primary Outcomes (1)

• Change in sCD14

  Change in plasma sCD14 concentration over 48 weeks

  Baseline, Week-4, -8, -12, -24, -36, -48

Secondary Outcomes (24)

• Marker of immune activation: Change in CD38

  baseline, Week-4, -8, -12, -24, -36 and -48

• Marker of immune activation: HLA-DR

  baseline, Week-4, -8, -12, -24, -36 and -48

• Marker of immune activation: Change in PD1

  baseline, Week-4, -8, -12, -24, -36 and -48

• Marker of immune activation: Change in CD169

  baseline, Week-4, -8, -12, -24, -36 and -48

• Marker of immune activation: Change in sCD163

  baseline, Week-4, -8, -12, -24, -36 and -48

Study Arms (3)

Methadone

EXPERIMENTAL

Participants in this arm will receive a 48-week integrated treatment program for opiate use disorder with daily directly observed oral methadone (MET) and antiretroviral therapy (cART).

Drug: Methadone

Buprenorphine/naloxone

EXPERIMENTAL

Participants in this arm will receive a 48-week integrated treatment program for opiate use disorder with daily directly observed oral buprenorphine/naloxone and antiretroviral therapy (cART).

Drug: Buprenorphine/naloxone

XR-Naltrexone

EXPERIMENTAL

Participants in this arm will receive a 48-week integrated treatment program for opiate use disorder with monthly injection extended-release naltrexone (XR-NTX) and antiretroviral therapy (cART).

Drug: XR-Naltrexone

Interventions

Methadone DRUG

Participants will receive a 48-week integrated treatment program for opiate use disorder with daily directly observed oral methadone syrup (MET), structured counseling sessions (BDRC-based) weekly for the first 3 months and monthly thereafter, and antiretroviral therapy.

Methadone

Buprenorphine/naloxone DRUG

Participants will receive a 48-week integrated treatment program for opiate use disorder with daily directly observed oral buprenorphine/naloxone tablets (Suboxone(R)), structured counseling sessions (BDRC-based) weekly for the first 3 months and monthly thereafter, and antiretroviral therapy.

Also known as: Suboxone

Buprenorphine/naloxone

XR-Naltrexone DRUG

Participants will receive a 48-week integrated treatment program for opiate use disorder with monthly extended-release naltrexone (Vivitrol(R)), structured counseling sessions (BDRC-based) weekly for the first 3 months and monthly thereafter, and antiretroviral therapy.

Also known as: Vivitrol

XR-Naltrexone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet DSM-5 criteria for moderate to severe opiate use disorder (as determined by DSM-5 checklist)
• Opiate use with a positive urine drug screen for heroin or other opiates (other than methadone, buprenorphine, buprenorphine/naloxone) at screening visit
• Documented HIV-1 infection with CD4 less than 350 cells/ μL and VL more than 10,000 copies/mL
• cART-naïve or or on cART no longer than 3 months if already started
• Willingness to receive cART or on cART no longer than 3 months if already started
• Willingness to be randomized to either daily methadone, buprenorphine/naloxone or monthly injection of extended-release naltrexone treatment
• Ability to understand and complete study procedures
• Provision of adequate locator information that lists all contact information a participant agrees that the research staff may use to reach him/her
• All participants must be able to comprehend the purpose of the study and to provide informed consent
• Is, in the opinion of the study physician, in stable health as determined by pre-study physical examination, medical history, ECG, and laboratory evaluations and is likely to complete the study.
• Has a total body weight of more than 50 kg (110 pounds) and a body mass index (BMI) of more than 20 at screening.
• Female subjects: Cannot be pregnant, Cannot be lactating, Must be unable to conceive (i.e., surgically sterilized, sterile, or post-menopausal defined as 1 year without bleeding or spotting) OR must agree to use an acceptable method of birth control (e.g., birth control pills, intrauterine device \[IUD\], or a double barrier method of birth control (condoms and spermicide together; or diaphragm, condom and spermicide together)

You may not qualify if:

• Current cognitive impairment, schizophrenia, paranoid disorder, bipolar disorder not compatible with study procedure (assessed by the medical director of the study)
• Known neurological, cardiovascular, renal, or other significant medical disorder that is likely to impair or make the individual's participation hazardous Active Tuberculosis or other symptomatic infectious disease AIDS-defining illness
• Current cancer or other malignancies
• Advanced liver disease (FibroScan® METAVIR score F3-F4, liver elasticity more than10kPa)
• Use of immunomodulators
• Meet DSM-5 criteria for any other substance use disorder (except nicotine)
• Engagement in opiate medication treatment at baseline (methadone, buprenorphine, buprenorphine/naloxone, naltrexone)
• Pending legal charges with likely incarceration within next 6 months
• Currently participating in another clinical trial

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute of Drug Abuse: collaborator
• The Wistar Institute: collaborator
• Institute of Applied Medicine and Epidemiology (IMEA): collaborator
• Ho Chi Minh City CDC: collaborator

Study Sites (2)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

ACTIVE NOT RECRUITING

Go Vap Clinic

Ho Chi Minh City, Vietnam

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders; Inflammation

Interventions

Methadone; Buprenorphine, Naloxone Drug Combination; vivitrol

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; Buprenorphine; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Luis J Montaner, DVM, D.Phil

  The Wistar Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David S Metzger, PhD

CONTACT

2157467346; dsm@pennmedicine.upenn.edu

Cecile M Denis, PhD

CONTACT

2158981825; cdenis@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will enroll 225 HIV-positive subjects who meet DSM-5 opiate use disorder criteria and who are using opiates (primarily heroin). All subjects will receive a 48-week integrated treatment program for opiate use disorder with either (randomly assigned) daily directly observed oral methadone (MET) and buprenorphine/naloxone (BUP/NX) or monthly injection extended-release naltrexone (XR-NTX).

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 21, 2020
• Study Start: January 30, 2023
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: July 11, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); VN (1)