Opiate Dependence
Conditions
Keywords
Opioid Addiction, Addiction, Drug Dependence
Brief summary
The purpose of this study is to evaluate a very low dose naltrexone-buprenorphine treatment to transfer opioid dependent individuals to extended release naltrexone injection (Vivitrol). The hypothesis is that patients will complete the transfer to Vivitrol successfully, finding the treatment acceptable and showing minimal withdrawal discomfort.
Detailed description
Thirty-five opioid dependent (OD) volunteers seeking treatment will be enrolled in an open-label, flexible-dosing, outpatient trial at Duke Addictions Program. On days 1-3, participants will receive buprenorphine/naloxone daily at a starting dose of 4mg, progressively decreasing to 2 mg on days 2- 3. Participants will also receive very low dose naltrexone (VLNTX) at a dose of 0.25 mg to 1mg on Days 1-3, 2 to 6 mg on Day 4 and between 10 and 50 mg on Days 5-7. Then a VIVITROL injection, 380 mg, will be administered on Day 8. Evaluations will occur daily for up to 6 hours until 1 day after VIVITROL injection and then weekly for 4 weeks. Patients will receive ancillary medications as needed and weekly psychosocial intervention. At the end of the study, participants will be offered outpatient treatment of OD at the study site, or will be referred to other treatment programs.
Interventions
DRUGvery low dose naltrexone
On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.
On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.
DRUGbuprenorphine/naloxone
On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.
Sponsors
Alkermes, Inc.
Paolo Mannelli
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women 18 to 65 years of age who meet DSM-IV criteria for OD of at least six months duration, supported by a positive urine for opiates and a positive naloxone challenge test if the diagnosis is unclear. 2. Individuals must be capable of giving informed consent and capable of complying with study procedures. 3. Participants will be asked to provide locator information including the address and telephone number of a non-drug abusing relative or friend who can reach the participant in emergencies.
Exclusion criteria
1. Individuals currently prescribed or regularly taking opiates for chronic pain or medical illness. 2. Individuals regularly using licit or illicit methadone or BUP. 3. Individuals meeting DSM-IV criteria for schizophrenia, schizoaffective or psychotic disorders, or psychiatric disorder (other than substance abuse) requiring intervention. 4. Individuals who are medically unstable, or have liver enzyme function tests greater than two times normal. 5. Individuals with current suicidal risk or 1 or more suicide attempts within the past year. 6. History of accidental drug overdose in the last three years or any other significant history of overdose following detoxification, defined as an episode of opioid-induced unconsciousness or incapacitation. 7. Nursing/pregnant women, or failure in a sexually active man or woman to use adequate contraceptive methods (e.g., oral or depot contraceptives, foam, sponges, and/or condoms) 8. Individuals who are dependent on any other drugs (excluding nicotine) 9. Individuals with known sensitivity to BUP, VIVITROL, NTX, naloxone. 10. Individuals who are court-mandated to treatment. 11. Individuals who have a current or pending legal status, or any other condition that would make them unlikely to be available for the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retention in Treatment | 4 weeks | After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Use of Ancillary Medications. | baseline to week 1 | Number of participants that took ancillary medication |
| Percentage of Participants With Adherence to Medication (Naltrexone) | Day 1 to Day 8 (+/- 2 days) | Participant who took Naltrexone as prescribed. |
| Withdrawal Intensity as Measured by the Clinical Opiate Withdrawal Scale (COWS) | 4 weeks | After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment. COWS rates eleven common opiate withdrawal signs or symptoms. The summed scores ranged from 0-48, with 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal. |
| Withdrawal Intensity as Measured by the Subjective Opiate Withdrawal Scale (SOWS) | 4 weeks | After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment. SOWS contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). Total score range is 0 - 64; the higher the score the more withdrawal symptoms. |
| Percentage of Participants Who Adhered to Study Visits. | baseline to end of study (approximately 40 days) | — |
| Illicit Drug Use, Measured by Urine Drug Testing | 4 weeks | number of participants that tested positive for marijuana, cocaine, and opiates. |
| Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire | Day 9 | Questionnaire consisted of 3 questions. 1. Were you satisfied with the treatment (range 1-5): Completely satisfied (1) to completely dissatisfied (5). 2. Were you satisfied with withdrawal treatment (range 1-5): Minimal withdrawal (1) to worse than ever (5). 3. Did the medication help (range 1-5): Helped a lot (1) to No it did not help (5). Lower scores represent greater satisfaction. |
| Number of Participants That Self Reported Illicit Drug Use | 4 weeks | Participants reported on any illicit drug use to include Cocaine marijuana opiates |
| Craving | 4 weeks | Craving, assessed with a 100-point Visual Analog Scale (VAS), ranging from 'not at all' (0) to 'more than ever' (100). The higher the score the higher the craving. |
Countries
United States
Participant flow
Recruitment details
38 participants signed consent. 3 participants were screen failures. 35 participants started study.
Participants by arm
| Arm | Count |
|---|---|
| BUP/VLNXT to VIVITROL | 35 |
| Total | 35 |
Baseline characteristics
| Characteristic | BUP/VLNXT to VIVITROL |
|---|---|
| Age, Continuous | 40.1 years |
| Race/Ethnicity, Customized African American | 26 participants |
| Race/Ethnicity, Customized Caucasian | 9 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 26 Participants |
| Years of Opioid use | 9.7 years |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 35 |
| serious Total, serious adverse events | 1 / 35 |
Outcome results
Primary
Retention in Treatment
After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks.
Time frame: 4 weeks
Population: All participants who received the Extended Release Injectable NTX
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BUP/VLNXT to VIVITROL | Retention in Treatment | 26 participants |
Secondary
Craving
Craving, assessed with a 100-point Visual Analog Scale (VAS), ranging from 'not at all' (0) to 'more than ever' (100). The higher the score the higher the craving.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BUP/VLNXT to VIVITROL | Craving | 5.12 units on a scale | Standard Deviation 14.41 |
Secondary
Illicit Drug Use, Measured by Urine Drug Testing
number of participants that tested positive for marijuana, cocaine, and opiates.
Time frame: 4 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BUP/VLNXT to VIVITROL | Illicit Drug Use, Measured by Urine Drug Testing | Cocaine | 3 participants |
| BUP/VLNXT to VIVITROL | Illicit Drug Use, Measured by Urine Drug Testing | Opiates | 4 participants |
| BUP/VLNXT to VIVITROL | Illicit Drug Use, Measured by Urine Drug Testing | Marijuana | 11 participants |
Secondary
Number of Participants That Self Reported Illicit Drug Use
Participants reported on any illicit drug use to include Cocaine marijuana opiates
Time frame: 4 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BUP/VLNXT to VIVITROL | Number of Participants That Self Reported Illicit Drug Use | Opiates | 4 participants |
| BUP/VLNXT to VIVITROL | Number of Participants That Self Reported Illicit Drug Use | Marijuana | 10 participants |
| BUP/VLNXT to VIVITROL | Number of Participants That Self Reported Illicit Drug Use | Cocaine | 3 participants |
Secondary
Percentage of Participants Who Adhered to Study Visits.
Time frame: baseline to end of study (approximately 40 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BUP/VLNXT to VIVITROL | Percentage of Participants Who Adhered to Study Visits. | 74 percentage of participants |
Secondary
Percentage of Participants With Adherence to Medication (Naltrexone)
Participant who took Naltrexone as prescribed.
Time frame: Day 1 to Day 8 (+/- 2 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BUP/VLNXT to VIVITROL | Percentage of Participants With Adherence to Medication (Naltrexone) | 100 percentage of participants |
Secondary
Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire
Questionnaire consisted of 3 questions. 1. Were you satisfied with the treatment (range 1-5): Completely satisfied (1) to completely dissatisfied (5). 2. Were you satisfied with withdrawal treatment (range 1-5): Minimal withdrawal (1) to worse than ever (5). 3. Did the medication help (range 1-5): Helped a lot (1) to No it did not help (5). Lower scores represent greater satisfaction.
Time frame: Day 9
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BUP/VLNXT to VIVITROL | Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire | Were you satisfied with the treatment | 1.31 units on a scale | Standard Deviation 0.84 |
| BUP/VLNXT to VIVITROL | Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire | Were you satisfied with withdrawal treatment | 2.04 units on a scale | Standard Deviation 0.82 |
| BUP/VLNXT to VIVITROL | Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire | Did the medication help | 1.69 units on a scale | Standard Deviation 0.93 |
Secondary
Use of Ancillary Medications.
Number of participants that took ancillary medication
Time frame: baseline to week 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BUP/VLNXT to VIVITROL | Use of Ancillary Medications. | 35 participants |
Secondary
Withdrawal Intensity as Measured by the Clinical Opiate Withdrawal Scale (COWS)
After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment. COWS rates eleven common opiate withdrawal signs or symptoms. The summed scores ranged from 0-48, with 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal.
Time frame: 4 weeks
Population: All participants who received the Extended Release Injectable NTX
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BUP/VLNXT to VIVITROL | Withdrawal Intensity as Measured by the Clinical Opiate Withdrawal Scale (COWS) | 0.64 units on a scale | Standard Deviation 1.29 |
Secondary
Withdrawal Intensity as Measured by the Subjective Opiate Withdrawal Scale (SOWS)
After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment. SOWS contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). Total score range is 0 - 64; the higher the score the more withdrawal symptoms.
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BUP/VLNXT to VIVITROL | Withdrawal Intensity as Measured by the Subjective Opiate Withdrawal Scale (SOWS) | 1.52 units on a scale | Standard Deviation 3.19 |