Neuromodulation of Trauma Memories in PTSD & Alcohol Dependence

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT01055171
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 44
• Location: 1
• Arms: 2
• Duration (Months): 31
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Dependence; PTSD	Drug: Propranolol; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment Implications of Trauma Memory Modulation for PTSD & Alcohol Dependence
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Propranolol Patients will receive Propranolol in this condition.	Drug: Propranolol; 40 mg; Single Administration.
Placebo Comparator: Placebo Patient to receive placebo in this condition.	Drug: Placebo; 40 mg; Single Dose.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MUSC	Charleston	South Carolina	United States	294258908

Sponsors and Collaborators

• Medical University of South Carolina
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Michael E Saladin, Ph.D., Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT01055171
• Other Study ID Numbers: 19489; 1RC1AA019019-01
• First Posted: Jan 25, 2010
• Last Update Posted: Mar 8, 2016
• Last Verified: Sep 1, 2012

• Keywords provided by Medical University of South Carolina: alcohol dependence; PTSD; propanolol; craving; beta-block; cue exposure; addiction; memory; trauma; addictive behavior
• Additional relevant MeSH terms: Alcoholism; Propranolol

Study Results

Participant Flow

Pre-assignment Detail	Participants were considered enrolled if they completed both the retrieval and testing procedure (44).

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Patients will receive Propranolol in this condition. Propranolol : 40 mg; Single Administration. The subjects analyzed who received propranolol were those that received the medication and completed both the test and retrieval sessions (Test Day 1 and 2).	Patient to receive placebo in this condition. Placebo : 40 mg; Single Dose. The subjects analyzed who received placebo were those that received the sugar pill and completed both the test and retrieval sessions (Test Day 1 and 2)
Period Title: Overall Study
STARTED	29	28
Retrieval Completion	25	24
Test Procedure Completion	21	23
COMPLETED	18	21
NOT COMPLETED	11	7

Baseline Characteristics

Arm/Group Title	Propranolol	Placebo	Total
Arm/Group Description	Patients will receive Propranolol in this condition. Propranolol: 40 mg; Single Administration.	Patient to receive placebo in this condition. Placebo: 40 mg; Single Dose.	Total of all reporting groups
Overall Participants	21	23	44
Age, Customized (Number) [Number]
Greater than or equal to 35 years	14 66.7%	17 73.9%	31 70.5%
Less than 35 years	7 33.3%	6 26.1%	13 29.5%
Sex: Female, Male (Count of Participants)
Female	9 42.9%	13 56.5%	22 50%
Male	12 57.1%	10 43.5%	22 50%

Outcome Measures

1. Primary Outcome

Title	Retrieval Session Distress Scores (Session 1)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Patients will receive Propranolol in this condition. Propranolol : 40 mg; Single Administration. The subjects analyzed who received propranolol were those that received the medication and completed both the test and retrieval sessions (Test Day 1 and 2).	Patient to receive placebo in this condition. Placebo : 40 mg; Single Dose. The subjects analyzed who received placebo were those that received the sugar pill and completed both the test and retrieval sessions (Test Day 1 and 2)
Measure Participants	21	23
Mean (Standard Error) [units on a scale]	54.5 (26.8)	73.9 (20.9)

2. Primary Outcome

Title	Retrieval Session Craving Scores (Session 1)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Patients will receive Propranolol in this condition. Propranolol : 40 mg; Single Administration. The subjects analyzed who received propranolol were those that received the medication and completed both the test and retrieval sessions (Test Day 1 and 2).	Patient to receive placebo in this condition. Placebo : 40 mg; Single Dose. The subjects analyzed who received placebo were those that received the sugar pill and completed both the test and retrieval sessions (Test Day 1 and 2)
Measure Participants	21	23
Mean (Standard Error) [units on a scale]	49.1 (31.3)	71.6 (20.4)

3. Primary Outcome

Title	Test Session Distress Scores (Session 2)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Patients will receive Propranolol in this condition. Propranolol : 40 mg; Single Administration. The subjects analyzed who received propranolol were those that received the medication and completed both the test and retrieval sessions (Test Day 1 and 2).	Patient to receive placebo in this condition. Placebo : 40 mg; Single Dose. The subjects analyzed who received placebo were those that received the sugar pill and completed both the test and retrieval sessions (Test Day 1 and 2)
Measure Participants	21	23
Mean (Standard Error) [units on a scale]	35.1 (3.7)	48.0 (3.5)

4. Primary Outcome

Title	Test Session Craving Scores (Session 2)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Patients will receive Propranolol in this condition. Propranolol : 40 mg; Single Administration. The subjects analyzed who received propranolol were those that received the medication and completed both the test and retrieval sessions (Test Day 1 and 2).	Patient to receive placebo in this condition. Placebo : 40 mg; Single Dose. The subjects analyzed who received placebo were those that received the sugar pill and completed both the test and retrieval sessions (Test Day 1 and 2)
Measure Participants	21	23
Mean (Standard Error) [units on a scale]	51.0 (3.7)	53.9 (3.5)

5. Secondary Outcome

Title	Proportion of Drinking Days
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Patients will receive Propranolol in this condition. Propranolol : 40 mg; Single Administration. The subjects analyzed who received propranolol were those that received the medication and completed both the test and retrieval sessions (Test Day 1 and 2).	Patient to receive placebo in this condition. Placebo : 40 mg; Single Dose. The subjects analyzed who received placebo were those that received the sugar pill and completed both the test and retrieval sessions (Test Day 1 and 2)
Measure Participants	21	23
Mean (Standard Error) [Drinking days]	42.2 (6.4)	45.9 (6.8)

Adverse Events

Arm/Group Title	Propranolol		Placebo
Arm/Group Description	Patients will receive Propranolol in this condition. Propranolol: 40 mg; Single Administration.		Patient to receive placebo in this condition. Placebo: 40 mg; Single Dose.
All Cause Mortality
	Propranolol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Propranolol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Propranolol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/26 (0%)

Limitations/Caveats

Lack of a "no retrieval" control group. Lack of determination of plasma propranolol levels following the medicated retrieval session. The sample size was insufficient to assess the more distal effects at 1-week follow-up.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.