Treatment Strategy to Prevent Mood Disorders Following Traumatic Brain Injury
NCT ID: NCT00704379
Last Updated: 2015-08-25
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2/PHASE3
94 participants
INTERVENTIONAL
2008-06-30
2014-04-30
Brief Summary
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Detailed Description
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The goals of this study are to learn more about how people recover from brain injury and to evaluate the effect of sertraline (also known as Zoloft) compared to placebo (an inactive substance) in preventing the occurrence of emotional and behavioral problems-such as depression, lack of motivation, anxiety, irritability or aggressive outbursts-following TBI.
In the study, a group of 104 participants with TBI-recruited immediately after resolution of posttraumatic amnesia-will be randomly assigned to receive six months of double-blind treatment with sertraline or placebo.
This study will determine how these emotional and behavioral problems influence thinking, physical recovery, and return to a productive life six months after brain injury. Researchers will also determine if certain brain changes can predict the occurrence of behavioral problems and if treatment with sertraline can prevent them. Additionally, the researchers will examine the effect of sertraline on frequent post-TBI behavioral disorders such as aggression, impulsivity, poor decision making and apathetic symptoms.
Magnetic resonance imaging (MRI)-based volumetry and diffusion tensor imaging will be used to examine the structural correlates of mood and anxiety disorders and to evaluate them as biological predictors of treatment response and community reintegration. The researchers hypothesize that early preventive treatment with sertraline will reduce mood and behavioral symptoms, prevent the occurrence of structural and functional brain changes associated with the onset of mood disorders, increase access to and participation in rehabilitation programs for TBI, and, consequently, improve psychosocial outcome.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
TRIPLE
Study Groups
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Placebo
Placebo will be given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.
Placebo
an inactive substance
Sertraline
Sertraline will be given in a double blind fashion via tablets administered once daily. Once stabilized in the targeted dosage (100 mg per day), sertraline serum levels will be monitored twice during the course of the intervention.
Sertraline
Sertraline and placebo will be given in a double blind fashion via an equal number of identical tablets administered once daily. Once stabilized in the targeted dosage (100 mg per day), sertraline serum levels will be monitored twice during the course of the intervention. Blood samples will be obtained randomly, one during the first and one during the second trimesters of the protocol.
Interventions
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Placebo
an inactive substance
Sertraline
Sertraline and placebo will be given in a double blind fashion via an equal number of identical tablets administered once daily. Once stabilized in the targeted dosage (100 mg per day), sertraline serum levels will be monitored twice during the course of the intervention. Blood samples will be obtained randomly, one during the first and one during the second trimesters of the protocol.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Meeting the Center for Disease Control (CDC) criteria for TBI.
* Mild, Moderate, or Severe TBI as categorized by initial Glasgow Coma Scale (GCS) scores 13 to 15, 9 to 12, or 3 to 8, respectively.
* Complete recovery from Post Traumatic Amnesia (PTA) within 4 weeks of the traumatic episode.
Exclusion Criteria
* Clinical or neuro-radiological evidence of associate spinal cord injury.
* Patients with severe comprehension deficits (i.e., those who are not able to complete part II of the Token Test) that precludes a thorough neuropsychiatric evaluation.
* Presence of Diagnostic and Statistical Manual IV defined mood, anxiety or psychotic disorder at the time of enrollment to the study. However, patients with a history of alcohol abuse or alcohol dependence during the year preceding TBI will be included in the study.
* Patients who were taking antidepressants at the time of TBI or during a six month period prior to the traumatic event.
* Patients who have failed an adequate previous trial with sertraline or had side effects that prompted the discontinuation of this medication.
* Pregnant women or women that plan to become pregnant during the period of the study.
* Severe complicating illness such as neoplastic disease or uncompensated heart, renal or liver failure.
18 Years
85 Years
ALL
No
Sponsors
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National Institute of Neurological Disorders and Stroke (NINDS)
NIH
Baylor College of Medicine
OTHER
Responsible Party
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Ricardo Jorge, MD
Professor
Principal Investigators
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Ricardo E. Jorge, MD
Role: PRINCIPAL_INVESTIGATOR
Baylor College of Medicine
Locations
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Baylor College of Medicine
Houston, Texas, United States
Countries
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References
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Arciniegas DB, Topkoff J, Silver JM. Neuropsychiatric Aspects of Traumatic Brain Injury. Curr Treat Options Neurol. 2000 Mar;2(2):169-186. doi: 10.1007/s11940-000-0017-y.
Fann JR, Burington B, Leonetti A, Jaffe K, Katon WJ, Thompson RS. Psychiatric illness following traumatic brain injury in an adult health maintenance organization population. Arch Gen Psychiatry. 2004 Jan;61(1):53-61. doi: 10.1001/archpsyc.61.1.53.
Silver JM, Hales RE, Yudofsky SC. Psychopharmacology of depression in neurologic disorders. J Clin Psychiatry. 1990 Jan;51 Suppl:33-9.
Jorge RE, Robinson RG, Moser D, Tateno A, Crespo-Facorro B, Arndt S. Major depression following traumatic brain injury. Arch Gen Psychiatry. 2004 Jan;61(1):42-50. doi: 10.1001/archpsyc.61.1.42.
Fann JR, Uomoto JM, Katon WJ. Sertraline in the treatment of major depression following mild traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2000 Spring;12(2):226-32. doi: 10.1176/jnp.12.2.226.
Graham DI, McIntosh TK, Maxwell WL, Nicoll JA. Recent advances in neurotrauma. J Neuropathol Exp Neurol. 2000 Aug;59(8):641-51. doi: 10.1093/jnen/59.8.641.
McIntosh TK, Saatman KE, Raghupathi R, Graham DI, Smith DH, Lee VM, Trojanowski JQ. The Dorothy Russell Memorial Lecture. The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms. Neuropathol Appl Neurobiol. 1998 Aug;24(4):251-67. doi: 10.1046/j.1365-2990.1998.00121.x.
Buki A, Povlishock JT. All roads lead to disconnection?--Traumatic axonal injury revisited. Acta Neurochir (Wien). 2006 Feb;148(2):181-93; discussion 193-4. doi: 10.1007/s00701-005-0674-4. Epub 2005 Dec 20.
Manji HK, Quiroz JA, Sporn J, Payne JL, Denicoff K, A Gray N, Zarate CA Jr, Charney DS. Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry. 2003 Apr 15;53(8):707-42. doi: 10.1016/s0006-3223(03)00117-3.
Warner-Schmidt JL, Duman RS. Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus. 2006;16(3):239-49. doi: 10.1002/hipo.20156.
Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006 Jun 15;59(12):1116-27. doi: 10.1016/j.biopsych.2006.02.013. Epub 2006 Apr 21.
Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science. 2003 Aug 8;301(5634):805-9. doi: 10.1126/science.1083328.
Normann C, Schmitz D, Furmaier A, Doing C, Bach M. Long-term plasticity of visually evoked potentials in humans is altered in major depression. Biol Psychiatry. 2007 Sep 1;62(5):373-80. doi: 10.1016/j.biopsych.2006.10.006. Epub 2007 Jan 19.
Sheline YI, Barch DM, Donnelly JM, Ollinger JM, Snyder AZ, Mintun MA. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry. 2001 Nov 1;50(9):651-8. doi: 10.1016/s0006-3223(01)01263-x.
Anand A, Li Y, Wang Y, Wu J, Gao S, Bukhari L, Mathews VP, Kalnin A, Lowe MJ. Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study. Neuropsychopharmacology. 2005 Jul;30(7):1334-44. doi: 10.1038/sj.npp.1300725.
Bechara A, Damasio H, Tranel D, Damasio AR. The Iowa Gambling Task and the somatic marker hypothesis: some questions and answers. Trends Cogn Sci. 2005 Apr;9(4):159-62; discussion 162-4. doi: 10.1016/j.tics.2005.02.002.
Huisman TA, Schwamm LH, Schaefer PW, Koroshetz WJ, Shetty-Alva N, Ozsunar Y, Wu O, Sorensen AG. Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury. AJNR Am J Neuroradiol. 2004 Mar;25(3):370-6.
Salmond CH, Menon DK, Chatfield DA, Williams GB, Pena A, Sahakian BJ, Pickard JD. Diffusion tensor imaging in chronic head injury survivors: correlations with learning and memory indices. Neuroimage. 2006 Jan 1;29(1):117-24. doi: 10.1016/j.neuroimage.2005.07.012. Epub 2005 Aug 9.
Le TH, Mukherjee P, Henry RG, Berman JI, Ware M, Manley GT. Diffusion tensor imaging with three-dimensional fiber tractography of traumatic axonal shearing injury: an imaging correlate for the posterior callosal
Jorge R, Robinson RG. Mood disorders following traumatic brain injury. NeuroRehabilitation. 2002;17(4):311-24. No abstract available.
Jorge RE, Robinson RG, Arndt S. Are there symptoms that are specific for depressed mood in patients with traumatic brain injury? J Nerv Ment Dis. 1993 Feb;181(2):91-9. doi: 10.1097/00005053-199302000-00004.
Jorge RE, Robinson RG, Arndt SV, Forrester AW, Geisler F, Starkstein SE. Comparison between acute- and delayed-onset depression following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 1993 Winter;5(1):43-9. doi: 10.1176/jnp.5.1.43.
Jorge RE, Robinson RG, Arndt SV, Starkstein SE, Forrester AW, Geisler F. Depression following traumatic brain injury: a 1 year longitudinal study. J Affect Disord. 1993 Apr;27(4):233-43. doi: 10.1016/0165-0327(93)90047-n.
Jorge RE, Robinson RG, Starkstein SE, Arndt SV. Depression and anxiety following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 1993 Fall;5(4):369-74. doi: 10.1176/jnp.5.4.369.
Jorge RE, Robinson RG, Starkstein SE, Arndt SV. Influence of major depression on 1-year outcome in patients with traumatic brain injury. J Neurosurg. 1994 Nov;81(5):726-33. doi: 10.3171/jns.1994.81.5.0726.
Jorge RE, Robinson RG, Starkstein SE, Arndt SV, Forrester AW, Geisler FH. Secondary mania following traumatic brain injury. Am J Psychiatry. 1993 Jun;150(6):916-21. doi: 10.1176/ajp.150.6.916.
Jorge R, Robinson RG. Mood disorders following traumatic brain injury. Int Rev Psychiatry. 2003 Nov;15(4):317-27. doi: 10.1080/09540260310001606700.
Jorge RE, Starkstein SE. Pathophysiologic aspects of major depression following traumatic brain injury. J Head Trauma Rehabil. 2005 Nov-Dec;20(6):475-87. doi: 10.1097/00001199-200511000-00001.
Tateno A, Jorge RE, Robinson RG. Pathological laughing and crying following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2004 Fall;16(4):426-34. doi: 10.1176/jnp.16.4.426.
Jorge RE, Acion L, Burin DI, Robinson RG. Sertraline for Preventing Mood Disorders Following Traumatic Brain Injury: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Oct 1;73(10):1041-1047. doi: 10.1001/jamapsychiatry.2016.2189.
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