Treatment Strategy to Prevent Mood Disorders Following Traumatic Brain Injury

NCT00704379 | Completed Phase 2 Results

• 2 other identifiers: R01NS0558271R01NS055827-01A2
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine the efficacy of sertraline to prevent the onset of mood and anxiety disorders during the first six months after traumatic brain injury.

Conditions

Traumatic Brain Injury

Keywords

traumatic brain injury; TBI; mood disorders; anxiety disorders; community reintegration; executive function; sertraline; diffusion tensor imaging

Outcome Measures

Primary Outcomes (1)

• Time to Onset of Diagnostic and Statistical Manual (DSM) IV Defined Mood and Anxiety Disorders Associated With Traumatic Brain Injury (TBI)

  Following the DSM-IV (now updated by the DSM-5), depressive disorders associated with TBI are categorized as Mood Disorder Due to Another Medical Condition with subtypes: 1) With major depressive-like episode (if the full criteria for a major depressive episode \[MDE\] are met) or 2) With depressive features (prominent depressed mood but full criteria for a MDE are not met); and 3) with mixed features (e.g. significant irritability, pressured speech and formal thought disorder). On the other hand, bipolar and related disorders due to TBI are subdivided in: 1) with manic or hypomanic like episode; 2) with manic features; and 3) with mixed features. A similar conceptual framework has been used to define Anxiety Disorder due to another Medical Condition, in this case, TBI. According to DSM-IV/DSM-5, such diagnosis can be made when, besides an evident pathophysiological relationship with TBI, panic attacks or generalized anxiety are the prominent features of the clinical presentation.

  6 months after TBI

Secondary Outcomes (5)

• Total Community Integration Questionnaire Scores

  6 months after TBI

• Iowa Gambling Task Score

  6 months after TBI

• Memory Function Composite

  6 months following traumatic brain injury

• Social Functioning Examination Total Score

  6 months after TBI

• Neuroimaging Variables (i.e., Fractional Anisotropy [FA] of Frontal White Matter Such as the Cingulate Gyrus)

  Baseline

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo will be given in a double blind fashion via an equal number of tablets (identical to the sertraline tablets) administered once daily.

Drug: Placebo

Sertraline

EXPERIMENTAL

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.

Drug: Sertraline

Interventions

Placebo DRUG

an inactive substance

Placebo

Sertraline DRUG

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.

Also known as: Zoloft

Sertraline

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or over.
• 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.

You may not qualify if:

• Penetrating head injuries.
• 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030-4211, United States

Location

Related Publications (30)

• 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.

  PMID: 11096746 BACKGROUND

• 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.

  PMID: 14706944 BACKGROUND

• Silver JM, Hales RE, Yudofsky SC. Psychopharmacology of depression in neurologic disorders. J Clin Psychiatry. 1990 Jan;51 Suppl:33-9.

  PMID: 2404002 BACKGROUND

• 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.

  PMID: 14706943 BACKGROUND

• 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.

  PMID: 11001601 BACKGROUND

• 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.

  PMID: 10952055 BACKGROUND

• 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.

  PMID: 9775390 BACKGROUND

• 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.

  PMID: 16362181 BACKGROUND

• 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.

  PMID: 12706957 BACKGROUND

• 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.

  PMID: 16425236 BACKGROUND

• 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.

  PMID: 16631126 BACKGROUND

• 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.

  PMID: 12907793 BACKGROUND

• 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.

  PMID: 17240361 BACKGROUND

• 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.

  PMID: 11704071 BACKGROUND

• 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.

  PMID: 15856081 BACKGROUND

• 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.

  PMID: 15808493 BACKGROUND

• 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.

  PMID: 15037457 BACKGROUND

• 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.

  PMID: 16084738 BACKGROUND

• 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

  BACKGROUND

• Jorge R, Robinson RG. Mood disorders following traumatic brain injury. NeuroRehabilitation. 2002;17(4):311-24. No abstract available.

  PMID: 12547979 BACKGROUND

• 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.

  PMID: 8426177 BACKGROUND

• 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.

  PMID: 8428134 BACKGROUND

• 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.

  PMID: 8509524 BACKGROUND

• 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.

  PMID: 8286933 BACKGROUND

• 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.

  PMID: 7931619 BACKGROUND

• 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.

  PMID: 8494069 BACKGROUND

• Jorge R, Robinson RG. Mood disorders following traumatic brain injury. Int Rev Psychiatry. 2003 Nov;15(4):317-27. doi: 10.1080/09540260310001606700.

  PMID: 15276953 BACKGROUND

• 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.

  PMID: 16304485 BACKGROUND

• 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.

  PMID: 15616168 BACKGROUND

• 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.

  PMID: 27626622 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; Mood Disorders; Anxiety Disorders

Interventions

Sertraline

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Mental Disorders

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Ricardo Jorge
• Organization: Baylor College of Medicine

Ricardo.Jorge@bcm.edu

713-794-7010

Study Officials

• Ricardo E. Jorge, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 20, 2008
• First Posted: June 24, 2008
• Study Start: June 1, 2008
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: August 25, 2015
• Results First Posted: May 12, 2015

Record last verified: 2015-08

Locations

US (1)