Opioid-Related DisordersPhase 4NEONCT01733693
Neurocognitive Effects of Opiate Agonist Treatment
A Phase 4 study testing Buprenorphine and Methadone in people with Opioid-Related Disorders and HIV, run by Albert Einstein College of Medicine at 2 sites in United States.
Trial summary
The purpose of this study is to (1) compare the effects of buprenorphine and methadone, two types of opioid addiction treatment, on the ability to think and reason among people addicted to opiates, and who are either HIV negative or HIV positive; and (2) investigate whether HIV infection changes the way opioid… Read more about this study
- Who is it for?
- Ages 18 to 68 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid-Related Disorders, HIV, HIV Infections
- What is being tested?
- Buprenorphine and Methadone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2013to Jun 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 68 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 - 68
- English or Spanish speaking
- Documentation of HIV Status
- Opioid-dependent without having received medication treatment for opioid dependence within the previous 90 days
- Negative pregnancy test, for women
- No "street" use of methadone or buprenorphine
Show all 10Show fewer
- Willing to participate in all study components
- Able to provide informed consent
- Education > 6 years
- Not acutely intoxicated
Who cannot join
- Serious or unstable medical disease: liver disease (AST or ALT ≥ 3x ULN, elevated PT/INR, albumin <3.0 g/dl or evidence of decompensated cirrhosis);
- Severe cardiovascular disease (MI, PTCA, unstable angina, CABG, and/or serious arrhythmia in the previous 6 months);
- COPD (requiring supplemental oxygen or hospitalization in past 6 months);
- End stage renal disease or creatinine clearance <30 mL/min
- Neurological disease: head injury with LOC>24 hour, previous penetrating skull wound, focal brain lesion, history of neurosurgery, seizure disorder (not ETOH-related), non-HIV CNS opportunistic infection
- Psychiatric disorders (schizophrenia or bipolar)
- Benzodiazepine or alcohol dependence
- Chronic pain conditions requiring opioid analgesics
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Fordham University
The Bronx, New York, 10458
Albert Einstein College of Medicine of Yeshiva University
The Bronx, New York, 10467
About this study
The purpose of this study is to (1) compare the effects of buprenorphine and methadone, two types of opioid addiction treatment, on the ability to think and reason among people addicted to opiates, and who are either HIV negative or HIV positive; and (2) investigate whether HIV infection changes the way opioid treatment affects the ability to think and reason. The investigators hypothesize that there will be (1) significant improvement in thinking and reasoning ability after starting buprenorphine treatment compared to methadone treatment, among participants with and without HIV at 2 and 4 months compared to baseline; and (2) HIV positive participants will demonstrate significant improvement in thinking and reasoning ability at 2 and 4 months compared to baseline, but that their thinking and reasoning ability will still be lower than HIV negative participants.
Read the detailed description
After randomization, each medication will be prescribed and administered by one of these experienced clinicians, according to well- established national protocols. Participants will be randomized in a 1:1 ratio in variable size blocks of 4-8 via central, computer-generated randomization. Given the relatively small sample size, we will randomize in blocks to ensure comparison groups of approximately equal size. Because medication type will not be blinded, we will vary block size to prevent anticipation of treatment arm assignment. We will also stratify randomization by HIV status to ensure equal numbers of HIV-infected persons in each arm.
INTERVENTION DOSE. Doses of buprenorphine and methadone will be adjusted within pre-specified ranges to ensure that comparisons between the two treatments are based on individually optimized doses.
Buprenorphine (we will use the buprenorphine/naloxone combination exclusively) will be administered at a dose of 8 to 32 mg per day, though we expect most subjects not to exceed 24 mg per day. These doses approximate methadone doses of 60 to 100 mg daily, which are in the upper range of doses generally used in clinical practice, but are well-known to be most efficacious and are also most prevalent in DoSA. Since study clinicians will be experienced substance abuse treatment providers, some flexibility will be allowed within these parameters. Both buprenorphine and methadone will be administered daily as oral medications.
The study will have two phases: induction/stabilization (weeks 1 - 3) and maintenance (weeks 4 - 24).
During dose induction/stabilization, subjects will attend daily visits (Sx/week) with a study clinician and receive gradually increasing doses of medication (see below). The first week of induction/stabilization will be considered a run-in period; at the conclusion of this week participants will complete enrollment in the trial and also complete their first NP research visit. The purpose of the run-in period is to ensure that we enroll persons who are able to comply with all trial requirements.
MAINTENANCE PHASE. The maintenance stage of opioid pharmacotherapy begins when a patient is responding optimally to medication treatment and routine dosage adjustments are no longer needed. Patients at this stage have stopped abusing opioids and many remain on the same dosage of treatment medication for many months, whereas others require frequent or occasional adjustments. During maintenance (starting on day 22, week 4),subjects in both arms will attend the clinic three times per week, on Monday, Wednesday, and Friday, and will receive bottles of medication to take home for the other four days of the week. Subjects will receive increases in their doses starting in week 4 if they meet pre-established criteria, up to 100 mg of methadone, and up to 32 mg of buprenorphine.
Our proposed research plan includes two follow-up visits, three and six months after the baseline visit. We anticipate that subjects will still be in the maintenance phase at the time of both these visits.
- Conditions
- Opioid-Related Disorders, HIV, HIV Infections
- Being tested
- Buprenorphine, Methadone
- Keywords
- Buprenorphine, Methadone, Cognition
- Medical subject headings
- Opioid-Related Disorders, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuprenorphineDrug
Also called Buprenorphine HCl
Study participants will be randomly assigned 1:1 to buprenorphine (experimental/intervention) or methadone (active comparator). We will stratify by HIV status to ensure an equal number of HIV-infected participants in each group.
MethadoneDrug
Also called Methadone Hydrochloride
Study participants will be randomly assigned 1:1 to buprenorphine (experimental/intervention) or methadone (active comparator). We will stratify by HIV status to ensure an equal number of HIV-infected participants in each group.
| Study group | Role | What they receive |
|---|---|---|
| Buprenorphine | Experimental | Oral sublingual tablet, 8-32 mg per day, administered daily for duration of 4 months Receives: Drug: Buprenorphine |
| Methadone | Active comparator | Oral sublingual tablet, 60-100 mg per day, administered daily for duration of 4 months Receives: Drug: Methadone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Global Neurocognitive Function
Metrics:
A Global Deficit Score (GDS) is computed by adding deficit ratings of the component test measures, and dividing by total number of measures. (Please see list of component test measures under the Domain-Specific Neurocognitive Function outcome).
Measured: 2 and 4 months
Domain-Specific Neurocognitive Function (i.e. in the domains of executive functioning, learning, memory, attention/working memory, processing speed, motor, and verbal functioning).
Metrics:
Domain Deficit Scores (DDS) are created for each of the 7 cognitive ability domains. Deficit Scores can be analyzed as dichotomous variables to classify individual subjects as impaired or normal, or continuously.
Executive Functioning -- Wisconsin Card Sorting Task-64 Item Version; Trail Making Test (Part B)
Learning -- Hopkins Verbal Learning Test-Revised (Total Recall); Brief Visuospatial Memory Test-Revised (Total Recall)
Memory -- Hopkins Verbal Learning Test (Delayed Recall Trial); Brief Visuospatial Memory Test-Revised (Delayed Recall Trial)
Attention/Working Memory -- WAIS-III Letter Number Sequencing; PASAT Total Correct
Processing Speed -- WAIS-III Digit Symbol; WAIS-III Symbol Search; Trail Making Test (Part A)
Motor -- Grooved Pegboard Time (dominant hand); Grooved Pegboard Time (non-dominant hand)]
Verbal Functioning -- Controlled Oral Word Association Test (F-A-S); Semantic (Animal) Fluency
Measured: 2 and 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2012 (estimated)
- Study startJan 2013
- Primary completionJun 2017
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid-Related DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albert Einstein College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), Montefiore Medical Center, Fordham University
- Responsible party
- Principal investigator, Julia H. Arnsten, Albert Einstein College of Medicine
- Investigators
- Julia Arnsten, MD, MPH, Principal investigator, Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01733693
- Sponsor's protocol ID
- 2012-433
- Other IDs
- 1R01DA032552-01A1
- Acronym
- NEO
- Status last verified
- Jan 2022
- First submitted
- 14 Nov 2012
- Last updated
- 11 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Scott TM, Arnsten J, Olsen JP, Arias F, Cunningham CO, Rivera Mindt M. Neurocognitive, psychiatric, and substance use characteristics in a diverse sample of persons with OUD who are starting methadone or buprenorphine/naloxone in opioid treatment programs. Addict Sci Clin Pract. 2021 Oct 24;16(1):64. doi: 10.1186/s13722-021-00272-4.
PubMed 34689841
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurocognitive Effects of Opiate Agonist Treatment
- ClinicalTrials.gov ID
- NCT01733693
- Acronym / sponsor ID
- NEO / 2012-433
- Conditions
- Opioid-Related Disorders, HIV, HIV Infections
- Keywords
- Buprenorphine, Methadone, Cognition
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- Albert Einstein College of MedicineUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), Montefiore Medical Center, Fordham University
- Study start
- Jan 2013
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 27 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to (1) compare the effects of buprenorphine and methadone, two types of opioid addiction treatment, on the ability to think and reason among people addicted to opiates, and who are either HIV negative or HIV positive; and (2) investigate whether HIV infection changes the way opioid treatment affects the ability to think and reason. The investigators hypothesize that there will be (1) significant improvement in thinking and reasoning ability after starting buprenorphine treatment compared to methadone treatment, among participants with and without HIV at 2 and 4 months compared to baseline; and (2) HIV positive participants will demonstrate significant improvement in thinking and reasoning ability at 2 and 4 months compared to baseline, but that their thinking and reasoning ability will still be lower than HIV negative participants.
Detailed description
After randomization, each medication will be prescribed and administered by one of these experienced clinicians, according to well- established national protocols. Participants will be randomized in a 1:1 ratio in variable size blocks of 4-8 via central, computer-generated randomization. Given the relatively small sample size, we will randomize in blocks to ensure comparison groups of approximately equal size. Because medication type will not be blinded, we will vary block size to prevent anticipation of treatment arm assignment. We will also stratify randomization by HIV status to ensure equal numbers of HIV-infected persons in each arm.
INTERVENTION DOSE. Doses of buprenorphine and methadone will be adjusted within pre-specified ranges to ensure that comparisons between the two treatments are based on individually optimized doses.
Buprenorphine (we will use the buprenorphine/naloxone combination exclusively) will be administered at a dose of 8 to 32 mg per day, though we expect most subjects not to exceed 24 mg per day. These doses approximate methadone doses of 60 to 100 mg daily, which are in the upper range of doses generally used in clinical practice, but are well-known to be most efficacious and are also most prevalent in DoSA. Since study clinicians will be experienced substance abuse treatment providers, some flexibility will be allowed within these parameters. Both buprenorphine and methadone will be administered daily as oral medications.
The study will have two phases: induction/stabilization (weeks 1 - 3) and maintenance (weeks 4 - 24).
During dose induction/stabilization, subjects will attend daily visits (Sx/week) with a study clinician and receive gradually increasing doses of medication (see below). The first week of induction/stabilization will be considered a run-in period; at the conclusion of this week participants will complete enrollment in the trial and also complete their first NP research visit. The purpose of the run-in period is to ensure that we enroll persons who are able to comply with all trial requirements.
MAINTENANCE PHASE. The maintenance stage of opioid pharmacotherapy begins when a patient is responding optimally to medication treatment and routine dosage adjustments are no longer needed. Patients at this stage have stopped abusing opioids and many remain on the same dosage of treatment medication for many months, whereas others require frequent or occasional adjustments. During maintenance (starting on day 22, week 4),subjects in both arms will attend the clinic three times per week, on Monday, Wednesday, and Friday, and will receive bottles of medication to take home for the other four days of the week. Subjects will receive increases in their doses starting in week 4 if they meet pre-established criteria, up to 100 mg of methadone, and up to 32 mg of buprenorphine.
Our proposed research plan includes two follow-up visits, three and six months after the baseline visit. We anticipate that subjects will still be in the maintenance phase at the time of both these visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Buprenorphine | Experimental | Drug: BuprenorphineOral sublingual tablet, 8-32 mg per day, administered daily for duration of 4 months |
| Methadone | Active comparator | Drug: MethadoneOral sublingual tablet, 60-100 mg per day, administered daily for duration of 4 months |
Who may qualify
- Ages
- 18 to 68 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age 18 - 68
- English or Spanish speaking
- Documentation of HIV Status
- Opioid-dependent without having received medication treatment for opioid dependence within the previous 90 days
- Negative pregnancy test, for women
Key exclusion criteria (8 listed)
- Serious or unstable medical disease: liver disease (AST or ALT ≥ 3x ULN, elevated PT/INR, albumin <3.0 g/dl or evidence of decompensated cirrhosis);
- Severe cardiovascular disease (MI, PTCA, unstable angina, CABG, and/or serious arrhythmia in the previous 6 months);
- COPD (requiring supplemental oxygen or hospitalization in past 6 months);
- End stage renal disease or creatinine clearance <30 mL/min
- Neurological disease: head injury with LOC>24 hour, previous penetrating skull wound, focal brain lesion, history of neurosurgery, seizure disorder (not ETOH-related), non-HIV CNS opportunistic infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BuprenorphineAlso: Buprenorphine HClStudy participants will be randomly assigned 1:1 to buprenorphine (experimental/intervention) or methadone (active comparator). We will stratify by HIV status to ensure an equal number of HIV-infected participants in each group. | Drug | Buprenorphine |
| MethadoneAlso: Methadone HydrochlorideStudy participants will be randomly assigned 1:1 to buprenorphine (experimental/intervention) or methadone (active comparator). We will stratify by HIV status to ensure an equal number of HIV-infected participants in each group. | Drug | Methadone |
Primary outcome
Global Neurocognitive Function
Time frame: 2 and 4 months
Metrics: A Global Deficit Score (GDS) is computed by adding deficit ratings of the component test measures, and dividing by total number of measures. (Please see list of component test measures under the Domain-Specific Neurocognitive Function outcome).
Domain-Specific Neurocognitive Function (i.e. in the domains of executive functioning, learning, memory, attention/working memory, processing speed, motor, and verbal functioning).
Time frame: 2 and 4 months
Metrics: Domain Deficit Scores (DDS) are created for each of the 7 cognitive ability domains. Deficit Scores can be analyzed as dichotomous variables to classify individual subjects as impaired or normal, or continuously. Executive Functioning -- Wisconsin Card Sorting Task-64 Item Version; Trail Making Test (Part B) Learning -- Hopkins Verbal Learning Test-Revised (Total Recall); Brief Visuospatial Memory Test-Revised (Total Recall) Memory -- Hopkins Verbal Learning Test (Delayed Recall Trial); Brief Visuospatial Memory Test-Revised (Delayed Recall Trial) Attention/Working Memory -- WAIS-III Letter Number Sequencing; PASAT Total Correct Processing Speed -- WAIS-III Digit Symbol; WAIS-III Symbol Search; Trail Making Test (Part A) Motor -- Grooved Pegboard Time (dominant hand); Grooved Pegboard Time (non-dominant hand)] Verbal Functioning -- Controlled Oral Word Association Test (F-A-S); Semantic (Animal) Fluency
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2022.
- Derived from this study: PubMed 34689841Scott TM, Arnsten J, Olsen JP, Arias F, Cunningham CO, Rivera Mindt M. Neurocognitive, psychiatric, and substance use characteristics in a diverse sample of persons with OUD who are starting methadone or buprenorphine/naloxone in opioid treatment programs. Addict Sci Clin Pract. 2021 Oct 24;16(1):64. doi: 10.1186/s13722-021-00272-4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julia Arnsten, MD, MPH principal investigator
Montefiore Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Buprenorphine and Methadone in people with Opioid-Related Disorders and HIV, run by Albert Einstein College of Medicine at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Global Neurocognitive Function (time frame: 2 and 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01733693, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2022.