HIV Infection, Alcohol Use, Pain
Conditions
Keywords
Alcohol Use, Pain, HIV, Low-dose naltrexone, Nalmefene
Brief summary
This study is a randomized controlled trial (RCT) to assess the feasibility, tolerability, and safety of using opioid receptor antagonists (naltrexone and nalmefene) to treat pain among HIV-infected persons with heavy alcohol use and chronic pain.
Detailed description
Pain is a common co-morbidity for HIV-infected patients. Prevalence studies suggest that, on average, half of all HIV-infected persons suffer pain. Chronic pain can lead to heavy alcohol use among HIV-infected persons, which may in turn be a barrier to treatment/control of HIV and contribute to spread of HIV. Thus there is an urgent need to address pain among persons with HIV. Opioid receptor antagonists such as naltrexone and nalmefene, which are licensed for treatment of alcohol use disorders, show promise as being effective and safe treatments for chronic pain among persons with HIV. This study will pilot test novel pharmacotherapies (opioid receptor antagonists) to improve chronic pain among HIV-infected heavy drinkers. The specific aims of the research is to assess the feasibility, tolerability and safety of using opioid receptor antagonists (low-dose naltrexone and nalmefene) to treat pain among HIV-infected persons with heavy alcohol use and chronic pain.
Interventions
4.5 mg of low dose naltrexone taken once daily for 8 weeks
DRUGNalmefene
18 mg of nalmefene taken once daily for 8 weeks
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Boston Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years or older * HIV-positive * Chronic pain (present ≥3 mo) of moderate to severe intensity * Heavy drinking past year (Based on NIAAA criteria: \> 14 standard drinks per week/ \> 4 drinks in a day for men; \> 7 drinks in the past week/ \> 3 drinks in a day for women) * If female, negative pregnancy test and willing to use adequate birth control * Provision of contact information for 2 contacts to assist with follow-up * Stable address within 100 kilometers of St. Petersburg * Possession of a telephone (home or cell) * Able and willing to comply with all study protocols and procedures
Exclusion criteria
* Not fluent in Russian * Cognitive impairment resulting in inability to provide informed consent based on research assessor (RA) assessment * Known active TB or current febrile illness * Breastfeeding * Uncontrolled psychiatric illness (such as active psychosis) (i.e., answered yes to any of the following: past three month active hallucinations; mental health symptoms prompting a visit to the ED or hospital) * History of hypersensitivity to naltrexone, nalmefene, or naloxone * Current use (past week) of illicit or prescribed opiates as documented by either self-report or positive urine drug test * Unwilling to abstain from opiates during the treatment period * Current use of neuroleptics * History of seizure disorder * Known liver failure * ALT/AST levels \>5x normal * History of Raynaud's Disease * Planned surgeries in the next three months * Enrolled in another HIV and/or substance use medication intervention study * Taking naltrexone in the past 30 days * Taking nalmefene in the past 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Medication Tolerability Measured Via a 0-100 Visual Analog Scale | Primary endpoint at 8 weeks | Medication tolerability will be measured via a 0-100 visual analog scale. Participants will be asked to indicate on a scale of 0-100, how well they have tolerated the study medication with 0 anchored as cannot tolerate at all and 100 as tolerate perfectly well. Higher numbers will be indicative of higher tolerability of the medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period | 4 weeks, 8 weeks | Measured via one question asking participants if they had discontinued medication since their last visit. Assessed at 4 and 8 week study visits. |
| Adherence to Medication Defined as Self-report of Percentage of Study Medication Taken in the Past Two Weeks | Endpoint at 8 weeks | Measured by participants' drawing a line on a a Visual Analog Scale, which ranges from 0 to 100. Higher numbers indicate higher adherence to study medication. |
| Number of Participants With Adherence Assessed Via Riboflavin in the Urine Confirming Adherence | Endpoint at 8 weeks | Measured through visual inspection of the urine for the presence or absence of riboflavin using ultraviolet (UV) light at the long wave setting (33 mm) in a room with low ambient light. |
| Change in Alcohol Use Defined as a Change in the Mean Number of Grams of Pure Ethanol Consumed Per Day From Baseline to 8 Weeks | Baseline, 8 weeks | Measured via 30 Day Alcohol Use Timeline Follow Back Method |
| Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction. | 4 weeks, 8 weeks | Measured via using the 14-item Treatment Satisfaction Questionnaire, which consists of 14 items that result in four domains: Effectiveness, Side Effects, Convenience and Global Satisfaction. Higher scores indicate greater satisfaction with medication. Assessed at 4 and 8 week study visits. |
| Severe Hepatotoxicity Defined as AST/ALT >10X the Level of Normal | Endpoint at 8 weeks | Aminotransferase levels (AST/ALT) are tested to look for severe hepatotoxicity defined as AST/ALT \> 10 times the level of normal. |
| Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question | 2 weeks, 4 weeks, 6 weeks, 8 weeks | Measured via a 16-item symptom checklist with the option for participants to report any experienced side effects not on the checklist. Side effect severity is rated by trained research assessors. The checklist is asked at 2, 4, 6, and 8-week study visits. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Naltrexone Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks | 8 |
| Nalmefene Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks | 3 |
| Total | 11 |
Baseline characteristics
| Characteristic | Low Dose Naltrexone | Nalmefene | Total |
|---|---|---|---|
| Age, Continuous | 38.3 years STANDARD_DEVIATION 7.46 | 35.7 years STANDARD_DEVIATION 1.09 | 37.8 years STANDARD_DEVIATION 7.02 |
| At risk drinking based on NIAAA criteria | 2 Participants | 1 Participants | 3 Participants |
| Cold pain threshold | 9.5 seconds | 10 seconds | 10 seconds |
| Cold pain tolerance | 19.3 seconds | 22 seconds | 19.5 seconds |
| Education (9 grades or more) | 8 Participants | 3 Participants | 11 Participants |
| Lifetime opioid use | 5 Participants | 3 Participants | 8 Participants |
| Married/Living with partner/In long-term relationship | 5 Participants | 3 Participants | 8 Participants |
| Pain interference | 2.5 units on a scale | 5.6 units on a scale | 4.1 units on a scale |
| Pain severity | 3.0 units on a scale | 4.5 units on a scale | 3.3 units on a scale |
| Past 30 day opioid use | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Russia | 8 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 3 |
| other Total, other adverse events | 3 / 8 | 3 / 3 |
| serious Total, serious adverse events | 1 / 8 | 0 / 3 |
Outcome results
Primary
Medication Tolerability Measured Via a 0-100 Visual Analog Scale
Medication tolerability will be measured via a 0-100 visual analog scale. Participants will be asked to indicate on a scale of 0-100, how well they have tolerated the study medication with 0 anchored as cannot tolerate at all and 100 as tolerate perfectly well. Higher numbers will be indicative of higher tolerability of the medication.
Time frame: Primary endpoint at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Naltrexone | Medication Tolerability Measured Via a 0-100 Visual Analog Scale | 90.7 score on a scale | Standard Deviation 22.4 |
| Nalmefene | Medication Tolerability Measured Via a 0-100 Visual Analog Scale | NA score on a scale | — |
Secondary
Adherence to Medication Defined as Self-report of Percentage of Study Medication Taken in the Past Two Weeks
Measured by participants' drawing a line on a a Visual Analog Scale, which ranges from 0 to 100. Higher numbers indicate higher adherence to study medication.
Time frame: Endpoint at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Naltrexone | Adherence to Medication Defined as Self-report of Percentage of Study Medication Taken in the Past Two Weeks | 87.5 score on a scale | Standard Deviation 35.4 |
| Nalmefene | Adherence to Medication Defined as Self-report of Percentage of Study Medication Taken in the Past Two Weeks | 0 score on a scale | Standard Deviation 0 |
Secondary
Change in Alcohol Use Defined as a Change in the Mean Number of Grams of Pure Ethanol Consumed Per Day From Baseline to 8 Weeks
Measured via 30 Day Alcohol Use Timeline Follow Back Method
Time frame: Baseline, 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose Naltrexone | Change in Alcohol Use Defined as a Change in the Mean Number of Grams of Pure Ethanol Consumed Per Day From Baseline to 8 Weeks | 5.5 grams of ethanol | Standard Deviation 10.1 |
| Nalmefene | Change in Alcohol Use Defined as a Change in the Mean Number of Grams of Pure Ethanol Consumed Per Day From Baseline to 8 Weeks | -6.83 grams of ethanol | Standard Deviation 9.7 |
Secondary
Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction.
Measured via using the 14-item Treatment Satisfaction Questionnaire, which consists of 14 items that result in four domains: Effectiveness, Side Effects, Convenience and Global Satisfaction. Higher scores indicate greater satisfaction with medication. Assessed at 4 and 8 week study visits.
Time frame: 4 weeks, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Naltrexone | Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction. | 4-Weeks | 47.3 score on a scale | Standard Deviation 24.4 |
| Low Dose Naltrexone | Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction. | 8-Weeks | 47.3 score on a scale | Standard Deviation 21.9 |
| Nalmefene | Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction. | 4-Weeks | 3.6 score on a scale | Standard Deviation 5.1 |
| Nalmefene | Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction. | 8-Weeks | 3.6 score on a scale | Standard Deviation 5.1 |
Secondary
Number of Participants With Adherence Assessed Via Riboflavin in the Urine Confirming Adherence
Measured through visual inspection of the urine for the presence or absence of riboflavin using ultraviolet (UV) light at the long wave setting (33 mm) in a room with low ambient light.
Time frame: Endpoint at 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Naltrexone | Number of Participants With Adherence Assessed Via Riboflavin in the Urine Confirming Adherence | 1 participants |
| Nalmefene | Number of Participants With Adherence Assessed Via Riboflavin in the Urine Confirming Adherence | 0 participants |
Secondary
Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question
Measured via a 16-item symptom checklist with the option for participants to report any experienced side effects not on the checklist. Side effect severity is rated by trained research assessors. The checklist is asked at 2, 4, 6, and 8-week study visits.
Time frame: 2 weeks, 4 weeks, 6 weeks, 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Low Dose Naltrexone | Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question | 2-Weeks | 1.5 number of side effects | Standard Deviation 1.6 |
| Low Dose Naltrexone | Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question | 4-Weeks | 1.3 number of side effects | Standard Deviation 1.2 |
| Low Dose Naltrexone | Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question | 6-Weeks | 0.9 number of side effects | Standard Deviation 1 |
| Low Dose Naltrexone | Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question | 8-Weeks | 0 number of side effects | Standard Deviation 0 |
| Nalmefene | Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question | 8-Weeks | 0 number of side effects | Standard Deviation 0 |
| Nalmefene | Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question | 2-Weeks | 4.5 number of side effects | Standard Deviation 6.4 |
| Nalmefene | Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question | 6-Weeks | 1.5 number of side effects | Standard Deviation 2.1 |
| Nalmefene | Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question | 4-Weeks | 1.5 number of side effects | Standard Deviation 2.1 |
Secondary
Severe Hepatotoxicity Defined as AST/ALT >10X the Level of Normal
Aminotransferase levels (AST/ALT) are tested to look for severe hepatotoxicity defined as AST/ALT \> 10 times the level of normal.
Time frame: Endpoint at 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Low Dose Naltrexone | Severe Hepatotoxicity Defined as AST/ALT >10X the Level of Normal | 0 participants |
| Nalmefene | Severe Hepatotoxicity Defined as AST/ALT >10X the Level of Normal | 0 participants |
Secondary
Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period
Measured via one question asking participants if they had discontinued medication since their last visit. Assessed at 4 and 8 week study visits.
Time frame: 4 weeks, 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Low Dose Naltrexone | Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period | 4-Weeks | 1 treatment discontinuations |
| Low Dose Naltrexone | Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period | 8-Weeks | 1 treatment discontinuations |
| Nalmefene | Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period | 8-Weeks | 2 treatment discontinuations |
| Nalmefene | Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period | 4-Weeks | 1 treatment discontinuations |