In this revised CDA-2 proposal, Dr. Orff proposes to study a behavioral therapeutic approach, Cognitive Behavioral Therapy for Insomnia (CBT-I) for veterans with a history of mild traumatic brain injury (mTBI) and current insomnia. There are three aims to this project: 1) determine the efficacy of CBT-I relative to Sleep Education in veterans with insomnia following mTBI; 2) evaluate sleep efficiency as a mediator of distal effects of CBT-I on symptoms of comorbid depression and PTSD and global functioning and disability; 3) examine the effects of moderator variables (e.g., depression, PTSD, physical pain) on CBT-I treatment outcomes. Dr. Orff plans to enroll 70 OEF/OIF/OND veterans who, following baseline assessments, will be randomly assigned to six weeks of either CBT-I or Sleep Education. The two conditions are matched appropriately for time and attention. These patients will be followed over the six weeks and assessed for changes in sleep and other outcomes. Applicant: Dr. Henry Orff has a 1988 BA in Health and Society and Psychology from University of Rochester, a 2010 PhD in Clinical Psychology from SDSU/UCSD, and post-doctoral appointments. He has been interested in sleep research since 1996 when he was a research assistant in a sleep lab. He lists 23 publications, seven of which are first authored. He was awarded a F31 NRSA pre-doctoral fellowship. He is at the right point in his career to pursue this CDA-2 award. Mentor/s: The mentoring team is excellent and well suited for Dr. Orff's purposes. All (except Dr. Golshan) are trained as clinical psychologists and all have written strong letters of endorsement. Elizabeth Twamley, PhD, will be the primary mentor for randomized clinical trials and rehabilitation of veterans with mTBI. She is Chief of the Neuropsychology Unit, Center of Excellence for Stress and Mental Health, and an Associate Professor of Psychiatry at UCSD. She has developed and tested two interventions for veterans with TBI. She is well funded and published and has good mentoring experience. She will meet weekly with Dr. Orff and devote 5% time. Philip Gehrman, PhD, will be the mentor for CBT-I and treatment fidelity. He is the Director of the Behavioral Sleep Medicine Program at the Philadelphia VAMC and Assistant Professor of Psychology in Psychiatry at U. Penn. He focuses on insomnia and is a national trainer for CBT-I. He is well published and also has good mentoring experience. He will meet with Dr. Orff by phone or skype and devote 5% time. Amy Jak, PhD, will serve as the mentor for mTBI and neuropsychology. She is the Director of TBI Cognitive Rehabilitation at the VA San Diego and an Assistant Professor of Psychiatry at UCSD. She is the co-director of the UCSD/VA psychology internship program. She is well published and has good mentoring experience. She will meet with the candidate monthly and devote 5% time. Sonia Ancoli-Israel, PhD., will serve as a mentor for behavioral sleep medicine and professional development. She is Professor Emeritus of Psychiatry and Medicine at UCSD and Director of the Gillin Sleep and Chronomedicine Research Center. She is certified in Behavioral Sleep Medicine. She has had a distinguished career and will meet with Dr. Orff monthly. Shahrokh Golshan, PhD, will provide biostatistics mentoring at 3% time. Training Program: Dr. Orff proposes a training program which will consist of clinical sleep training, TBI training, RCT training, and professional development training. He will accomplish this through a combination of mentoring, coursework, and attendance at local conferences and national meetings. These training goals and the approach described are appropriate. Significance: To date, there are no studies of CBT-I in this population. Given the relatively high prevalence of mTBI in younger veterans and the high co-occurrence of sleep disturbance with both mTBI and psychiatric disorders such as depression and PTSD, this is an important study that could potentially benefit many veterans in VA care. Furthermore, it is a non-pharmaceutical approach, thereby offering an alternative to potentially harmful and addictive regimens. Approach: The approach is a sound one, and considerably improved compared with the previous application. There are just a few issues that are troublesome. 1) Dr. Orff plans on randomizing subjects in order to keep the research assistant (who will be doing the evaluations) blind. It is good that the research assistant will not be randomizing; however, ideally a third party (neither assessor nor interventionist) should be doing the randomization to ensure that there is no cherry picking of the subjects. 2) It was unclear who would deliver the control condition. These individuals should be matched to the CBT-I interventionists as much as possible (e.g., education level, experience). 3) Please describe how the insomnia diagnosis (main study inclusion variable) will be made. Environment: The environment is excellent, especially the sleep lab which will be used for baseline and outcome assessments. Feasibility: There should be no problem recruiting the 70 veterans who will be enrolled in this study. Dr. Orff is an excellent candidate for this CDA-2 award. He has considerably improved this revised application and has assembled an outstanding mentoring team. Given his extensive experience with sleep research, he is at the right stage of his career to pursue this award.
The aims of this study are straightforward, and the study design follows accordingly. The four issues of concern are relatively minor and easily fixed. Ethical/Safety Issues: The applicant is willing to provide CBT-I to control patients without delay at the completion of their participation in the program. While this is admirable and may help recruitment, it is not ethical to do so until after the results have been analyzed from all subjects. It is presumptuous to assume that CBT-I will be superior to Sleep Education (after all, that's why the study is being conducted). Clinical Relevance: Insomnia and mTBI are common among younger veterans. Improving sleep could have salutary effects on conditions that frequently co-occur with mTBI, such as PTSD and depression, as well as functioning and disability. Additionally, as a non-pharmaceutical approach, it is likely safer than medications with no risk of addiction and fewer side effects. Budget: No concerns Other Issues: None

Public Health Relevance

Many Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn era Veterans have suffered a mild traumatic brain injury (mTBI), and now cope with multiple post- injury symptoms, including sleep disturbances (especially insomnia). Chronic insomnia in mTBI patients has the potential to exacerbate other symptoms, delay recovery, and negatively affect many of the cognitive, psychological, and neuromuscular sequelae of mTBI, thereby decreasing quality of life. Although Cognitive-Behavioral Therapy for Insomnia (CBT-I) has been shown to be an effective evidence-based treatment for insomnia, there are no published randomized controlled trials evaluating the potential strengths and/or limitations of CBT-I in post-mTBI patients. Therefore, assessing CBT-I in the context of mTBI holds promise to provide substantial benefits in terms of improved rehabilitation outcomes in Veterans who have suffered mTBI.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (IK2)
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Career Development Program - Panel II (RRD9)
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VA San Diego Healthcare System
San Diego
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Olsen, Donald C; Hays, Chelsea C; Orff, Henry J et al. (2018) Correlates of employment and postsecondary education enrolment in Afghanistan and Iraq veterans with traumatic brain injuries. Brain Inj 32:544-549
Colvonen, Peter J; Glassman, Lisa H; Crocker, Laura D et al. (2017) Pretreatment biomarkers predicting PTSD psychotherapy outcomes: A systematic review. Neurosci Biobehav Rev 75:140-156
Kaufmann, Christopher N; Orff, Henry J; Moore, Raeanne C et al. (2017) Psychometric Characteristics of the Insomnia Severity Index in Veterans With History of Traumatic Brain Injury. Behav Sleep Med :1-9
Schiehser, Dawn M; Delano-Wood, Lisa; Jak, Amy J et al. (2017) Predictors of cognitive and physical fatigue in post-acute mild-moderate traumatic brain injury. Neuropsychol Rehabil 27:1031-1046