Alcohol Dependence, Post-Traumatic Stress Disorder (PTSD)
Conditions
Keywords
Alcohol Dependence, Post-Traumatic Stress Disorder (PTSD), Zonisamide, Cognitive Processing Therapy (CPT)
Brief summary
This is a randomized, controlled trial with 50 veterans diagnosed with post-traumatic stress disorder (PTSD) and comorbid alcohol dependence. Veterans will be randomized to receive either zonisamide (400 mg) or placebo for 12 weeks in a double blind fashion. Randomization will be done using 3:1 ratio and will be performed by our research pharmacy using a random assignment in blocks of 4- 3 will be assigned to active medication and 1 to placebo. Medication will be titrated over a 6 week titration phase followed by a 6 week treatment phase. All veterans will receive E-CPT-C therapy for the 12 weeks of treatment; E-CPT-C will be provided by trained and qualified clinicians with extensive experience providing E-CPT-C. Veterans will be recruited primarily through advertisement, but also through the clinical facilities at the VA and from other collaborators.
Interventions
BEHAVIORALEnhanced-Cognitive Processing Therapy-C (E-CPT-C)
DRUGZonisamide
DRUGPlacebo
Sponsors
United States Department of Defense
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Current alcohol dependence, as determined by a structured clinical interview (Structured Clinical Interview for DSM-IV Axis I Disorders) (SCID) * Current PTSD as determined by a structured clinical interview (SCID) * Veterans with current alcohol dependence, with at least one recent episode of heavy drinking over the past 14 days. * Medically and neurologically healthy on the basis of history, physical examination, EKG, screening laboratories * For women, negative pregnancy test and use of acceptable method of contraception
Exclusion criteria
* Females who are pregnant or lactating. * Veterans with a current unstable medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology, which in the opinion of the physician would preclude the subject from fully cooperating or be of potential harm during the course of the study * Veterans who meet current SCID criteria for a major Axis I diagnosis (Bipolar Disorders, Schizophrenia and Schizophrenia-type Disorders). * History of substance dependence (other than alcohol, tobacco or cannabis) by DSM-IV criteria in the last 90 days. * Veterans taking mood stabilizers and antipsychotic medications for specific psychiatric disorders. * Veterans with a history of allergy to zonisamide. * Veterans already receiving CPT.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Drinking Days | 12 weeks | Using a 90 day Timeline Follow Back (TLFB), the total number of drinking days at baseline and at 12 weeks of treatment were used. |
| Number of Heavy Drinking Days | 12 weeks | Timeline Follow Back (TLFB) will be used to document the number of heavy drinking days during 12 weeks of treatment. Heavy drinking is defined as greater than or equal to 5 drinks for men and greater than or equal to 4 drinks for women. |
| Clinician-Administered PTSD Scale (CAPS) Total Score | 12 weeks | The Clinician-Administered PTSD Scale (CAPS) Total Score will be used to measure PTSD symptoms at the end of the 12 week intervention. The CAPS Total Score is a summing of the 17 items that are each scored 0-4- where 0 indicates none. The range of Total Scores can be 0 to 136, where 136 would be the highest amount of scored PTSD symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zonisamide Participants in this arm will receive zonisamide for 12 weeks.
Enhanced-Cognitive Processing Therapy-C (E-CPT-C)
Zonisamide | 18 |
| Placebo Participants in this arm will receive placebo medication for 12 weeks.
Enhanced-Cognitive Processing Therapy-C (E-CPT-C)
Placebo | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Zonisamide | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 44.28 years STANDARD_DEVIATION 12.94 | 47.83 years STANDARD_DEVIATION 11.57 | 45.17 years STANDARD_DEVIATION 12.46 |
| Race/Ethnicity, Customized African American | 7 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Caucasian | 7 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Hispanic | 4 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United States | 18 participants | 6 participants | 24 participants |
| Sex: Female, Male Female | 18 Participants | 4 Participants | 22 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 6 |
| other Total, other adverse events | 6 / 18 | 2 / 6 |
| serious Total, serious adverse events | 1 / 18 | 2 / 6 |
Outcome results
Primary
Clinician-Administered PTSD Scale (CAPS) Total Score
The Clinician-Administered PTSD Scale (CAPS) Total Score will be used to measure PTSD symptoms at the end of the 12 week intervention. The CAPS Total Score is a summing of the 17 items that are each scored 0-4- where 0 indicates none. The range of Total Scores can be 0 to 136, where 136 would be the highest amount of scored PTSD symptoms.
Time frame: 12 weeks
Population: The intention to treat population was used in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zonisamide | Clinician-Administered PTSD Scale (CAPS) Total Score | Baseline | 67.33 units on a scale | Standard Error 5.49 |
| Zonisamide | Clinician-Administered PTSD Scale (CAPS) Total Score | 12 weeks | 30.83 units on a scale | Standard Error 6.02 |
| Placebo | Clinician-Administered PTSD Scale (CAPS) Total Score | Baseline | 72.83 units on a scale | Standard Error 9.51 |
| Placebo | Clinician-Administered PTSD Scale (CAPS) Total Score | 12 weeks | 23.80 units on a scale | Standard Error 11.21 |
Primary
Number of Drinking Days
Using a 90 day Timeline Follow Back (TLFB), the total number of drinking days at baseline and at 12 weeks of treatment were used.
Time frame: 12 weeks
Population: The intention to treat population was used in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zonisamide | Number of Drinking Days | Baseline | 46.87 days | Standard Error 5.63 |
| Zonisamide | Number of Drinking Days | 12 weeks | 7.44 days | Standard Error 5.47 |
| Placebo | Number of Drinking Days | Baseline | 51.00 days | Standard Error 9.48 |
| Placebo | Number of Drinking Days | 12 weeks | 17.33 days | Standard Error 9.48 |
Primary
Number of Heavy Drinking Days
Timeline Follow Back (TLFB) will be used to document the number of heavy drinking days during 12 weeks of treatment. Heavy drinking is defined as greater than or equal to 5 drinks for men and greater than or equal to 4 drinks for women.
Time frame: 12 weeks
Population: The intention to treat population was used in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zonisamide | Number of Heavy Drinking Days | Baseline | 43.94 days | Standard Error 5.37 |
| Zonisamide | Number of Heavy Drinking Days | 12 weeks | 5.50 days | Standard Error 5.22 |
| Placebo | Number of Heavy Drinking Days | Baseline | 31.50 days | Standard Error 9.05 |
| Placebo | Number of Heavy Drinking Days | 12 weeks | 4.16 days | Standard Error 9.05 |