Candidate Daryl Shorter, M.D. is a Staff Psychiatrist at Michael E. DeBakey VA Medical Center (MEDVAMC), Medical Director of the Outpatient Clinical Trials Research (OCTR) program, and Assistant Professor of Psychiatry at Baylor College of Medicine (BCM) who has served as co-investigator for studies addressing medication development for treatment of disorders such as cocaine dependence and PTSD. Dr. Shorter believes the quality of addictions treatment for veterans can be improved by evaluating novel medications for addictions treatment through clinical trials, and using pharmacogenetics to identify subpopulations of patients who will best respond to treatment. In the short-term, Dr. Shorter hopes to obtain mentored grant support through the VA CDA in order to (1) hone skills necessary to design and execute medication clinical trials for addictions and pharmacogenetics, and (2) generate pilot data to obtain independent funding. In the long-term, Dr. Shorter hopes to conduct prospective multisite trials for addictions treatment, employing pharmacogenetics, and bringing novel agents into clinical practice. Environment The research proposed in this CDA will take place in the OCTR program located at MEDVAMC. Directed by primary mentor, Thomas R. Kosten, M.D., the OCTR conducts medication trials for treatment of psychiatric and addictive disorders. Given the affiliation of OCTR with Menninger Department of Psychiatry and BCM, and its location in the Texas Medical Center, this environment offers an extensive network of academic and research institutions and study populations Research The educational objectives of the CDA will be met through completion of the outpatient, randomized double-blind, placebo controlled trial of doxazosin, an alpha-1 adrenergic antagonist, for treatment of cocaine addiction. This 17-week trial will randomize 150 participants onto either doxazosin 8mg/day or placebo;subjects will present to OCTR thrice weekly for urine drug screen and completion of research activities. All participants will receive manual-guided cognitive behavioral therapy. The a priori primary outcome is reduction in percentage of cocaine positive urines. Secondary outcomes include reduction in Hamilton Anxiety Rating Scale scores, retention, and safety/tolerability. Also, a blood sample will be collected from each participant consenting to genetic analysis. The training plan begins with management of the Doxazosin RCT and data analysis, first using a frequentist, and following with a Bayesian, statistical approach. During phase II, time spent in the genetics lab will provide learning of pharmacogenetics techniques;after which, genetic subgroup analysis using both frequentist and Bayesian approaches will be performed. During phases III and IV, adaptive research design skills will be learned, with preparation of a protocol comparing two compounds (doxazosin versus another medication) for cocaine treatment. This protocol will be used as the basis for a merit review grant.

Public Health Relevance

Cocaine use disorders affect approximately 1.5 million Americans annually, and next to alcohol, is the second most common substance use disorder in the VA system. Cocaine use is associated with worsening of medical and psychiatric illnesses, particularly anxiety disorders such as Post Traumatic Stress Disorder. Currently, there are no US Food and Drug Administration approved medications for treatment of cocaine dependence;however, both animal and human studies suggest that medications affecting the noradrenergic system can reduce cocaine craving and use. We will study the effect of doxazosin, an alpha-1 adrenergic antagonist, in reducing cocaine use and anxiety symptoms among cocaine-dependent individuals. In addition, we will identify genetic subpopulations of participants who preferentiall respond to the medication.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (IK2)
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Clinical Trials (CLIN)
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Michael E Debakey VA Medical Center
United States
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Shorter, Daryl; Nielsen, David A; Hamon, Sara C et al. (2016) The ?-1 adrenoceptor (ADRA1A) genotype moderates the magnitude of acute cocaine-induced subjective effects in cocaine-dependent individuals. Pharmacogenet Genomics 26:428-35
Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R (2016) Buprenorphine Prescribing: To Expand or Not to Expand. J Psychiatr Pract 22:183-92
Ayanga, Daniel; Shorter, Daryl; Kosten, Thomas R (2016) Update on pharmacotherapy for treatment of opioid use disorder. Expert Opin Pharmacother 17:2307-2318
Mathai, David S; Verrico, Christopher D; Shorter, Daryl et al. (2016) ""Just one bad high:"" considering synthetic cannabinoid outcome expectancies in adolescents. Am J Addict :
Shorter, Daryl; Domingo, Coreen B; Kosten, Thomas R (2015) Emerging drugs for the treatment of cocaine use disorder: a review of neurobiological targets and pharmacotherapy. Expert Opin Emerg Drugs 20:15-29
Shorter, Daryl; Hsieh, John; Kosten, Thomas R (2015) Pharmacologic management of comorbid post-traumatic stress disorder and addictions. Am J Addict 24:705-12
Billups, Dana; Shorter, Daryl (2015) Needs assessment survey of addictions training in general psychiatry residency. Am J Addict 24:191-2
Li, Xiaofan; Shorter, Daryl; Kosten, Thomas R (2014) Buprenorphine in the treatment of opioid addiction: opportunities, challenges and strategies. Expert Opin Pharmacother 15:2263-75