Alcohol Dependence, PTSD
Conditions
Keywords
alcohol dependence, PTSD, propanolol, craving, beta-block, cue exposure, addiction, memory, trauma, addictive behavior
Brief summary
The purpose of this study is to examine the effect of propranolol versus placebo on craving, distress and cue reactivity to trauma and alcohol cues.
Detailed description
Summary and Synthesis: Epidemiological studies have established the occurrence of high rates of AD in persons with PTSD. Likewise, studies of alcohol/drug abuse treatment seekers have documented high rates of trauma exposure and PTSD. The high prevalence of PTSD/AD comorbidity is the cause of enormous human suffering, most of which either goes untreated or is resistant to treatment efforts. Both theory and research concerning the interface between these two disorders suggests that PTSD is associated with the initiation of excessive alcohol use and/or the development of AD by way of an escape/avoidance behavioral mechanism wherein escalating alcohol use is reinforced by its ability to dampen the negative emotions and arousal associated with PTSD. If PTSD is often a primary cause of the initiation and maintenance of AD, then clinical interventions that primarily impact PTSD should lead to significant improvements in craving for, and use of, alcohol. The findings of two recent treatment studies offer especially compelling support for this expectation. Drawing on both basic neuroscience research and a developing body of suggestive clinical/applied research, we were led to consider if the putative memory modulating properties of the adrenergic antagonist propranolol might have therapeutic benefits for PTSD/AD comorbid individuals. Thus, the proposed study will test the hypothesis that the strategic administration of propranolol coupled with the elicitation/retrieval of trauma-related memories will dampen emotional distress, alcohol craving and cue reactivity during subsequent exposure to trauma- and alcohol-related cues. A two-week follow-up laboratory session and clinical assessment will permit us to evaluate whether treatment benefits are maintained over time and if there are any changes in alcohol use and PTSD symptomatology.
Interventions
DRUGPropranolol
40 mg; Single Administration.
DRUGPlacebo
40 mg; Single Dose.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants must meet DSM-IV criteria for current alcohol dependence * Participants must have experienced criminal victimization * Use of birth control by female participants * Live within a 50-mile radius of research site * Consent to remain abstinent of all drugs and alcohol for 24 hours prior to patient admission and follow-up * Consent to random assignment to propanol or placebo * Individuals must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
Exclusion criteria
* Women who are pregnant, nursing or are of childbearing potential and not using birth control. * Evidence or history of significant hematological, endocrine, cardiovascular, pulmonary, renal, gastrointestinal or neurological disease * Significant liver impairment * Currently taking anti-arrhythmic agents, psychostimulants or other agents known to interfere with heart rate and skin conductance monitoring. * Known or suspected hypersensitivity to propanol * Individuals taking medication that could adversely interact with the study medication, including the following: albuterol, insulin or significant inhibitors of CYP2D6 * Individuals with bronchial asthma or chronic obstructive pulmonary disease * Prospective participants will be excluded if they are currently receiving exposure-based therapy for PTSD. * Individuals with a history of or current psychotic disorder. * Individuals with Addison's disease, Cushing's disease or other diseases of the adrenal cortex likely to affect cortisol levels. * Individuals receiving synthetic glucocorticoid therapy, any exogenous therapy, or treatment with other agents that interfere with HPA axis function within one month of the time of testing. * Individuals with resting heart rates less than 55 bpm.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retrieval Session Distress Scores (Session 1) | Multiple times throughout cue exposure during retrieval session (Session 1) | Found by using our Single Item Distress (SID) scale. A study team member asks the participant to verbally report the level of distress they were experiencing using values between 0 and 100, with 0 representing no distress and 100 extreme distress. |
| Retrieval Session Craving Scores (Session 1) | Multiple times throughout cue exposure during retrieval session (Session 1) | Found by using our Single Item Craving (SIC) scale. A study team member asks the participant to verbally report the level of craving they were experiencing using values between 0 and 100, with 0 representing no craving and 100 extreme craving for alcohol. |
| Test Session Distress Scores (Session 2) | Multiple times throughout cue exposure during test session (Session 2) | Found by using our Single Item Distress (SID) scale. A study team member asks the participant to verbally report the level of distress they were experiencing using values between 0 and 100, with 0 representing no distress and 100 extreme distress. |
| Test Session Craving Scores (Session 2) | Multiple times throughout cue exposure during test session (Session 2) | Found by using our Single Item Craving (SIC) scale. A study team member asks the participant to verbally report the level of craving they were experiencing using values between 0 and 100, with 0 representing no craving and 100 extreme craving for alcohol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Drinking Days | 90 days prior to participation in study up to 2-week follow up session (Session 3) | Proportion of drinking days from 90 days prior to the screening to the follow-up period. |
Countries
United States
Participant flow
Pre-assignment details
Participants were considered enrolled if they completed both the retrieval and testing procedure (44).
Participants by arm
| Arm | Count |
|---|---|
| Propranolol Patients will receive Propranolol in this condition.
Propranolol: 40 mg; Single Administration. | 21 |
| Placebo Patient to receive placebo in this condition.
Placebo: 40 mg; Single Dose. | 23 |
| Total | 44 |
Baseline characteristics
| Characteristic | Propranolol | Placebo | Total |
|---|---|---|---|
| Age, Customized Greater than or equal to 35 years | 14 Participants | 17 Participants | 31 Participants |
| Age, Customized Less than 35 years | 7 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Female | 9 Participants | 13 Participants | 22 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 26 |
| serious Total, serious adverse events | 0 / 25 | 0 / 26 |
Outcome results
Primary
Retrieval Session Craving Scores (Session 1)
Found by using our Single Item Craving (SIC) scale. A study team member asks the participant to verbally report the level of craving they were experiencing using values between 0 and 100, with 0 representing no craving and 100 extreme craving for alcohol.
Time frame: Multiple times throughout cue exposure during retrieval session (Session 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol | Retrieval Session Craving Scores (Session 1) | 49.1 units on a scale | Standard Error 31.3 |
| Placebo | Retrieval Session Craving Scores (Session 1) | 71.6 units on a scale | Standard Error 20.4 |
Primary
Retrieval Session Distress Scores (Session 1)
Found by using our Single Item Distress (SID) scale. A study team member asks the participant to verbally report the level of distress they were experiencing using values between 0 and 100, with 0 representing no distress and 100 extreme distress.
Time frame: Multiple times throughout cue exposure during retrieval session (Session 1)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol | Retrieval Session Distress Scores (Session 1) | 54.5 units on a scale | Standard Error 26.8 |
| Placebo | Retrieval Session Distress Scores (Session 1) | 73.9 units on a scale | Standard Error 20.9 |
Primary
Test Session Craving Scores (Session 2)
Found by using our Single Item Craving (SIC) scale. A study team member asks the participant to verbally report the level of craving they were experiencing using values between 0 and 100, with 0 representing no craving and 100 extreme craving for alcohol.
Time frame: Multiple times throughout cue exposure during test session (Session 2)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol | Test Session Craving Scores (Session 2) | 51.0 units on a scale | Standard Error 3.7 |
| Placebo | Test Session Craving Scores (Session 2) | 53.9 units on a scale | Standard Error 3.5 |
Primary
Test Session Distress Scores (Session 2)
Found by using our Single Item Distress (SID) scale. A study team member asks the participant to verbally report the level of distress they were experiencing using values between 0 and 100, with 0 representing no distress and 100 extreme distress.
Time frame: Multiple times throughout cue exposure during test session (Session 2)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol | Test Session Distress Scores (Session 2) | 35.1 units on a scale | Standard Error 3.7 |
| Placebo | Test Session Distress Scores (Session 2) | 48.0 units on a scale | Standard Error 3.5 |
Secondary
Proportion of Drinking Days
Proportion of drinking days from 90 days prior to the screening to the follow-up period.
Time frame: 90 days prior to participation in study up to 2-week follow up session (Session 3)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propranolol | Proportion of Drinking Days | 42.2 Drinking days | Standard Error 6.4 |
| Placebo | Proportion of Drinking Days | 45.9 Drinking days | Standard Error 6.8 |