Leveraging Biomarkers for Personalized Treatment of Alcohol Use Disorder Comorbid With PTSD
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|ClinicalTrials.gov Identifier: NCT03667846|
Recruitment Status : Recruiting
First Posted : September 12, 2018
Last Update Posted : February 5, 2021
|Condition or disease||Intervention/treatment||Phase|
|Post Traumatic Stress Disorder Alcohol Use Disorder||Drug: Topiramate Other: Placebo||Phase 2|
Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are highly comorbid, and present a clinical challenge for which existing treatments have limited efficacy. Existing clinical evidence suggests treatments that simultaneously address symptoms of both PTSD and AUD should be more efficacious than treating either disorder in isolation. The overlap in the neurobiological basis of PTSD and AUD (involving alterations in incentive salience, stress/negative affect, and executive control network functioning) suggests that there could be treatments that would effectively treat both disorders. However, there is no pharmacotherapy or psychotherapy treatment that is clearly effective for both disorders.
Topiramate, an FDA-approved anticonvulsant with effects on GABAergic and glutamatergic signaling, has demonstrated efficacy in the treatment of AUD in several randomized clinical trials (RCTs), and has also been tested in several open-label and small RCTs for treatment of PTSD with some evidence of effectiveness. Positive results in one open-label trial and one small RCT in patients with co-occurring PTSD and AUD suggest that topiramate may have beneficial effects on symptoms of both PTSD and AUD in this population. Preclinical work also supports the efficacy of topiramate in ameliorating anxiety-like behavior and altered stress response in animal models of stress and chronic alcohol exposure. A recent clinical study demonstrated that the effects of topiramate on alcohol use were moderated by a polymorphism of the GRIK1 gene (coding for the kainate receptor GluK1 subunit), such that significant benefit was found only among rs2832407 C-allele homozygotes.
This trial is designed to contrast acute and persisting effects of topiramate to those of placebo treatment in a sample of 150 participants with comorbid PTSD and moderate to severe AUD, and to evaluate the moderating effect of rs2832407 genotype on medication effects. Drug will be titrated over 8 weeks to a maximum dose of 200 mg and continued for 4 more weeks for a total of 12 weeks of treatment, followed by a 2-week taper. Alcohol and PTSD-related outcomes will be assessed at multiple time points throughout the study. Plasma biomarkers and neuropsychological assessments will be obtained at baseline and at week 12. In support of the overall aims of the center focusing on personalized medicine, the trial will serve as a platform for studies of topiramate's effects on brain chemistry and function as measured by fMRI, and EEG . Data from this clinical trial will also contribute to Overall Center Aims investigating the relationship of plasma biomarkers to neuroimaging markers.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Leveraging Biomarkers for Personalized Treatment of Alcohol Use Disorder Comorbid With Post Traumatic Stress Disorder|
|Actual Study Start Date :||October 16, 2019|
|Estimated Primary Completion Date :||April 2023|
|Estimated Study Completion Date :||April 2023|
Placebo Comparator: Placebo
Placebo tablets will be encapsulated in identical capsules.
Week 0-1: 25 mg qhs Week 1-2: 25 mg qAM, 25 mg qhs Week 2-3: 25 mg qAM, 50 mg qhs Week 3-4: 50 mg qAM, 50 mg qhs Week 4-5: 50 mg qAM, 75 mg qhs Week 5-6: 75 mg qAM, 75 mg qhs Week 6-7: 75 mg qAM, 100 mg qhs Week 7-8: 100 mg qAM, 100 mg qhs Week 8-10: 100 mg qAM, 100 mg qhs Week 10-12: 100 mg qAM, 100 mg qhs Week 12-14: 2-week taper
Generic topiramate, FDA-approve for clinical use, will be purchased in 25mg, 50mg, and 100mg strengths, and encapsulated.
Other Name: Topamax
- Measure of Time-line Follow-back (TLFB) [ Time Frame: Day 1 ]Retrospective estimate of daily alcohol consumption over a time period ranging from 7 days to 24 months prior to initial interview
- Percent Day Abstinent from Alcohol [ Time Frame: Week 9 to Week 12 ]Percentage of day abstinent from alcohol between week 9 and week 12
- PCL-5 score [ Time Frame: Week 9 to Week 12 ]20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. The symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items. Each question is measured on a 5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range - 0-80; 80 being more severe) can be obtained by summing the scores for each of the 20 items.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03667846
|Contact: Duna Abu-Amara, MPH||(646) 754-4793||Duna.Abu-Amara@nyulangone.org|
|Contact: Michael Bogenschutz, MD||(646) 501-4026||Michael.Bogenschutz@nyulangone.org|
|United States, New York|
|New York University School of Medicine||Recruiting|
|New York, New York, United States, 10016|
|Contact: Duna Abu Amara 646-754-4793 Duna.Abu-Amara@nyulangone.org|
|Principal Investigator: Charles Marmar, MD|
|Principal Investigator:||Charles Marmar, MD||NYU Langone Health|