Alcohol Dependence, Alcoholism, Post-Traumatic Stress Disorder
Conditions
Keywords
Alcoholism, Alcohol Dependence, Post-Traumatic Stress Disorder, Naltrexone, Cognitive Behavior Therapy
Brief summary
This study will evaluate naltrexone and cognitive-behavioral therapy treatments for alcohol dependence and post-traumatic stress disorder (PTSD). Subjects will be randomly assigned a 6-month treatment of either: 1) naltrexone alone, 2) naltrexone with PTSD psychosocial therapy, 3) a placebo with PTSD psychosocial therapy, or 4) placebo alone. An enhanced medication management intervention will accompany all treatment conditions. Follow-up assessments will be completed at 9 and 12 months after treatment.
Interventions
BEHAVIORALCognitive-Behavioral Therapy
Twelve weekly 90-minute individual therapy sessions followed by (6) 90-minute sessions every other week
DRUGNaltrexone
Daily dosing 100 mg for 24 weeks
DRUGPlacebo
Pill Placebo daily dosing 24 weeks
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Meets criteria for alcohol dependence and post-traumatic stress disorder. * Heavy drinking in the past 30 days (an average of more than 12 alcohol drinks per week with at least 1 day of 4 or more drinks). * Successfully complete medical detoxification. * Exhibit clinically significant trauma-related symptoms. * Live in a commutable distance to the University of Pennsylvania and agree to follow-up visits. * Aged between 18 and 65 years old. * Able to provide an informed consent. * Speak and read English.
Exclusion criteria
* Current diagnosis of any substance dependence other than alcohol, nicotine, or cannabis. * Evidence of opiate use in the past 30 days. * Significant risk of violence or history of serious violent behavior during the past year. * Continued contact with an intimate partner if assault by the partner is the index trauma. * Changes in dosage or medication for any SSRI treatment in the three months prior to entering the study. * Unstable or serious medical illness. * Current severe psychiatric symptom. * Mental retardation or another pervasive developmental disorder. * Use of an investigational medication in the past 30 days. * Pregnant, nursing or not using reliable contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Week 0 (Pretreatment), Week 24 (Posttreatment), Week 52 (Follow-up) | The PSS-I-IV is a clinician-rated interview that evaluates PTSD symptoms on a frequency/severity scale corresponding to the DSM-IV symptom criteria. The measure has a total score range from 0 to 51, with higher scores indicating more severe PTSD symptoms. |
| Drinking Timeline Follow-back Interview (TFBI) | Week 0 (Pretreatment), Week 24 (Posttreatment), Week 52 (Follow-up) | The TFBI is an interview that utilizes a calendar method to assess when and how much alcohol was consumed by the participant. At Week 0 (Pretreatment), Week 24 (Posttreatment), and Week 52 (Follow-up), alcohol consumed in the past 90 days was assessed. This measure was then used to calculate the percentage of days drinking in the past 90 days at each time point. Higher scores for percentage of days drinking indicate worse drinking outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Penn Alcohol Cravings Scale | Week 0 (Pretreatment), Week 24 (Posttreatment), Week 52 (Follow-up) | The Penn Alcohol Craving Scale is a 5-item self-report measure. It assesses alcohol craving during the prior week. Total scores on this measure range from 0 to 30, with higher scores indicating a higher level of craving. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Naltrexone + Supportive Counseling Naltrexone alone
Naltrexone: Daily dosing 100 mg for 24 weeks | 42 |
| Naltrexone + CBT (Prolonged Exposure Therapy) Naltrexone with CBT for PTSD
Cognitive-Behavioral Therapy: Twelve weekly 90-minute individual therapy sessions followed by (6) 90-minute sessions every other week
Naltrexone: Daily dosing 100 mg for 24 weeks | 40 |
| Placebo + CBT (Prolonged Exposure Therapy) Placebo with CBT for PTSD
Cognitive-Behavioral Therapy: Twelve weekly 90-minute individual therapy sessions followed by (6) 90-minute sessions every other week | 40 |
| Placebo + Supportive Counseling Placebo alone
Placebo: Pill Placebo daily dosing 24 weeks | 43 |
| Total | 165 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 4 | 3 |
| Overall Study | Death | 0 | 0 | 0 | 1 |
| Overall Study | Scheduling Conflict | 0 | 3 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 9 | 9 | 6 |
Baseline characteristics
| Characteristic | Naltrexone + CBT (Prolonged Exposure Therapy) | Naltrexone + Supportive Counseling | Total | Placebo + Supportive Counseling | Placebo + CBT (Prolonged Exposure Therapy) |
|---|---|---|---|---|---|
| Age, Continuous | 40.1 years | 44.9 years | 42.7 years | 41.2 years | 44.7 years |
| Race/Ethnicity, Customized Black | 30 Participants | 21 Participants | 105 Participants | 26 Participants | 28 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 2 Participants | 7 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Native American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 19 Participants | 50 Participants | 14 Participants | 8 Participants |
| Region of Enrollment United States | 40 Participants | 42 Participants | 165 Participants | 43 Participants | 40 Participants |
| Sex: Female, Male Female | 13 Participants | 16 Participants | 57 Participants | 15 Participants | 13 Participants |
| Sex: Female, Male Male | 27 Participants | 26 Participants | 108 Participants | 28 Participants | 27 Participants |
| Types of trauma Combat | 4 Participants | 4 Participants | 19 Participants | 4 Participants | 7 Participants |
| Types of trauma Other | 8 Participants | 9 Participants | 42 Participants | 15 Participants | 10 Participants |
| Types of trauma Physical Assault | 16 Participants | 18 Participants | 62 Participants | 16 Participants | 12 Participants |
| Types of trauma Sexual Assault | 12 Participants | 11 Participants | 42 Participants | 8 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 42 | 21 / 40 | 22 / 40 | 18 / 43 |
| serious Total, serious adverse events | 3 / 42 | 2 / 40 | 4 / 40 | 3 / 43 |
Outcome results
Primary
Drinking Timeline Follow-back Interview (TFBI)
The TFBI is an interview that utilizes a calendar method to assess when and how much alcohol was consumed by the participant. At Week 0 (Pretreatment), Week 24 (Posttreatment), and Week 52 (Follow-up), alcohol consumed in the past 90 days was assessed. This measure was then used to calculate the percentage of days drinking in the past 90 days at each time point. Higher scores for percentage of days drinking indicate worse drinking outcomes.
Time frame: Week 0 (Pretreatment), Week 24 (Posttreatment), Week 52 (Follow-up)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Naltrexone + Supportive Counseling | Drinking Timeline Follow-back Interview (TFBI) | Pretreatment (Week 0) | 75.4 percentage of days |
| Naltrexone + Supportive Counseling | Drinking Timeline Follow-back Interview (TFBI) | Follow-up (Week 52) | 21.5 percentage of days |
| Naltrexone + Supportive Counseling | Drinking Timeline Follow-back Interview (TFBI) | Posttreatmwent (Week 24) | 3.5 percentage of days |
| Naltrexone + CBT (Prolonged Exposure Therapy) | Drinking Timeline Follow-back Interview (TFBI) | Follow-up (Week 52) | 8.8 percentage of days |
| Naltrexone + CBT (Prolonged Exposure Therapy) | Drinking Timeline Follow-back Interview (TFBI) | Posttreatmwent (Week 24) | 7.3 percentage of days |
| Naltrexone + CBT (Prolonged Exposure Therapy) | Drinking Timeline Follow-back Interview (TFBI) | Pretreatment (Week 0) | 71.2 percentage of days |
| Placebo + CBT (Prolonged Exposure Therapy) | Drinking Timeline Follow-back Interview (TFBI) | Posttreatmwent (Week 24) | 13.4 percentage of days |
| Placebo + CBT (Prolonged Exposure Therapy) | Drinking Timeline Follow-back Interview (TFBI) | Follow-up (Week 52) | 18.9 percentage of days |
| Placebo + CBT (Prolonged Exposure Therapy) | Drinking Timeline Follow-back Interview (TFBI) | Pretreatment (Week 0) | 78.6 percentage of days |
| Placebo + Supportive Counseling | Drinking Timeline Follow-back Interview (TFBI) | Follow-up (Week 52) | 27.3 percentage of days |
| Placebo + Supportive Counseling | Drinking Timeline Follow-back Interview (TFBI) | Pretreatment (Week 0) | 74.1 percentage of days |
| Placebo + Supportive Counseling | Drinking Timeline Follow-back Interview (TFBI) | Posttreatmwent (Week 24) | 13.2 percentage of days |
Primary
Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV)
The PSS-I-IV is a clinician-rated interview that evaluates PTSD symptoms on a frequency/severity scale corresponding to the DSM-IV symptom criteria. The measure has a total score range from 0 to 51, with higher scores indicating more severe PTSD symptoms.
Time frame: Week 0 (Pretreatment), Week 24 (Posttreatment), Week 52 (Follow-up)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Naltrexone + Supportive Counseling | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Pretreatment (Week 0) | 27.1 units on a scale |
| Naltrexone + Supportive Counseling | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Follow-up (Week 52) | 10.9 units on a scale |
| Naltrexone + Supportive Counseling | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Posttreatmwent (Week 24) | 15.3 units on a scale |
| Naltrexone + CBT (Prolonged Exposure Therapy) | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Pretreatment (Week 0) | 30.3 units on a scale |
| Naltrexone + CBT (Prolonged Exposure Therapy) | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Follow-up (Week 52) | 7.9 units on a scale |
| Naltrexone + CBT (Prolonged Exposure Therapy) | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Posttreatmwent (Week 24) | 12.2 units on a scale |
| Placebo + CBT (Prolonged Exposure Therapy) | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Posttreatmwent (Week 24) | 13.3 units on a scale |
| Placebo + CBT (Prolonged Exposure Therapy) | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Pretreatment (Week 0) | 27.7 units on a scale |
| Placebo + CBT (Prolonged Exposure Therapy) | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Follow-up (Week 52) | 10.8 units on a scale |
| Placebo + Supportive Counseling | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Pretreatment (Week 0) | 27.5 units on a scale |
| Placebo + Supportive Counseling | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Follow-up (Week 52) | 11.1 units on a scale |
| Placebo + Supportive Counseling | Posttraumatic Stress Disorder (PTSD) Symptom Scale - Interview (PSS-I-IV) | Posttreatmwent (Week 24) | 15.5 units on a scale |
Secondary
Penn Alcohol Cravings Scale
The Penn Alcohol Craving Scale is a 5-item self-report measure. It assesses alcohol craving during the prior week. Total scores on this measure range from 0 to 30, with higher scores indicating a higher level of craving.
Time frame: Week 0 (Pretreatment), Week 24 (Posttreatment), Week 52 (Follow-up)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Naltrexone + Supportive Counseling | Penn Alcohol Cravings Scale | Follow-up (Week 52) | 7.4 percentage of days |
| Naltrexone + Supportive Counseling | Penn Alcohol Cravings Scale | Posttreatmwent (Week 24) | 8.0 percentage of days |
| Naltrexone + Supportive Counseling | Penn Alcohol Cravings Scale | Pretreatment (Week 0) | 17.7 percentage of days |
| Naltrexone + CBT (Prolonged Exposure Therapy) | Penn Alcohol Cravings Scale | Posttreatmwent (Week 24) | 5.1 percentage of days |
| Naltrexone + CBT (Prolonged Exposure Therapy) | Penn Alcohol Cravings Scale | Pretreatment (Week 0) | 17.9 percentage of days |
| Naltrexone + CBT (Prolonged Exposure Therapy) | Penn Alcohol Cravings Scale | Follow-up (Week 52) | 6.0 percentage of days |
| Placebo + CBT (Prolonged Exposure Therapy) | Penn Alcohol Cravings Scale | Pretreatment (Week 0) | 19.2 percentage of days |
| Placebo + CBT (Prolonged Exposure Therapy) | Penn Alcohol Cravings Scale | Posttreatmwent (Week 24) | 9.1 percentage of days |
| Placebo + CBT (Prolonged Exposure Therapy) | Penn Alcohol Cravings Scale | Follow-up (Week 52) | 6.9 percentage of days |
| Placebo + Supportive Counseling | Penn Alcohol Cravings Scale | Posttreatmwent (Week 24) | 10.3 percentage of days |
| Placebo + Supportive Counseling | Penn Alcohol Cravings Scale | Follow-up (Week 52) | 8.9 percentage of days |
| Placebo + Supportive Counseling | Penn Alcohol Cravings Scale | Pretreatment (Week 0) | 18.7 percentage of days |