Evaluation of Capsulotomy by Linear Accelerator Radiosurgery in Severe and Refractory Obsessive-compulsive Disorder

Quality of Life Clinical Trial

Official title:

Initial Evaluation of Efficacy and Adverse Events of Single Lesions in Bilateral Ventral-capsular and Ventral Capsulotomy-striatal by Linear Accelerator Radiosurgery in Severe and Refractory Obsessive-compulsive Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02500888
• Other study ID #: 14-0341
• Status: Recruiting
• Phase: N/A
• Start date: June 30, 2015
• Est. completion date: June 30, 2022

Study information

• Verified date: February 2021
• Source: Hospital de Clinicas de Porto Alegre
• Contact: Paulo Abreu, M.D.; Ph.D.
• Phone: 555133598294
• Email: paulo.abreu[@]ufrgs.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate, through a pilot study with about ten cases, if bilateral ventral capsulotomy by linear accelerator enable modification of obsessive-compulsive symptoms and quality of life in patients with severe and refractory obsessive compulsive disorder (OCD) and also investigate possible adverse effects / complications of the procedure.

Description:

About ten patients with severe and refractory OCD will receive bilateral single lesions at the bottom of the anterior limb of the internal capsule by linear accelerator. Prior to the procedure, a detailed clinical and psychiatric evaluation, plus an extensive battery of psychiatric diagnostic tests, severity and progression of OCD, depression / anxiety symptoms, presence of tics, psychosocial impairment, quality of life, familial accommodation and neuropsychological and personality testes will be performed. Furthermore, the patients will be also assessed by serological and neuroimaging tests. The Individuals will be periodically evaluated and followed up for one year. The results of the scores of the rating scales will be analyzed and compared, as well as the profile of adverse events, cognitive or personality changes and improves in clinical tests and neuroimaging studies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. OCD diagnosis, according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as a major disease entity. If comorbidity with other psychiatric or personality disorders, OCD symptoms dominate the clinical picture and precede other disorders.

2. Duration of OCD symptoms of at least five years.

3. Scores range of the obsessive-compulsive symptoms "Yale-Brown Obsessive-Compulsive Scale" (YBOCS) greater than 26 (or greater than 13, if obsessions or compulsions alone).

4. Fill up the criteria for refractory to prior treatments.

5. Be accepted by the method of "best estimate" for defining the patient is refractory, which consisted of confirmation by at least two specialists obsessive-compulsive disorder that the patient fulfills the criteria for effective refractory to previous treatments.

Exclusion Criteria:

1. History of head trauma or post-traumatic amnesia.

2. Background of systemic or neurological diseases with brain impairment, severe and active.

3. History of current use of substances capable of inducing psychopathological manifestations, or signs of cumulative effects of alcohol or drugs in the central nervous system (such as cortical atrophy), confirmed by neuroimaging.

4. pregnancy or lactation.

5. Refusal to submit to the radiosurgical procedure.

6. Refusal to accept the informed consent form, or participate.

7. History of mental retardation and / or inability to understand the informed consent, confirmed by neuropsychological tests of the initial evaluation.

8. Lack of family or companion with proper capacity of understanding of the informed consent in patients with comorbid major depression or psychosis that could potentially have difficulty performing the appropriate judgment as to participate in the study.

Related Conditions & MeSH terms

• Obsessive-Compulsive Disorder
• OCD
• Quality of Life

Intervention

Radiation:
• Radiosurgery
Only one radiation session of about 180 Gy in bilateral internal capsule.

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul

Sponsors (1)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre

Country where clinical trial is conducted

Brazil, 

References & Publications (37)

Asberg M, Montgomery SA, Perris C, Schalling D, Sedvall G. A comprehensive psychopathological rating scale. Acta Psychiatr Scand Suppl. 1978;(271):5-27. — View Citation

Ballantine HT Jr, Cassidy WL, Flanagan NB, Marino R Jr. Stereotaxic anterior cingulotomy for neuropsychiatric illness and intractable pain. J Neurosurg. 1967 May;26(5):488-95. — View Citation

Batistuzzo MC, Taub A, Nakano E, D'Alcante CC, de Mathis ME, Hoexter MQ, Miguel EC, Lopes AC. Performance of patients with refractory obsessive-compulsive disorder in the Frontal Systems Behavior Scale. Neurocase. 2009;15(2):157-62. doi: 10.1080/13554790802709047. Epub 2009 Mar 9. — View Citation

Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol. 1988 Dec;56(6):893-7. — View Citation

BECK AT, WARD CH, MENDELSON M, MOCK J, ERBAUGH J. An inventory for measuring depression. Arch Gen Psychiatry. 1961 Jun;4:561-71. — View Citation

Brandt RA, Salvajoli JV, Oliveira VC, Carmignani M, da Cruz JC, Leal HD, Ferraz L. [Linear accelerator radiosurgery]. Arq Neuropsiquiatr. 1995 Mar;53(1):38-45. Portuguese. — View Citation

Calvocoressi L, Libman D, Vegso SJ, McDougle CJ, Price LH. Global functioning of inpatients with obsessive-compulsive disorder, schizophrenia, and major depression. Psychiatr Serv. 1998 Mar;49(3):379-81. — View Citation

Calvocoressi L, Mazure CM, Kasl SV, Skolnick J, Fisk D, Vegso SJ, Van Noppen BL, Price LH. Family accommodation of obsessive-compulsive symptoms: instrument development and assessment of family behavior. J Nerv Ment Dis. 1999 Oct;187(10):636-42. — View Citation

Cecconi JP, Lopes AC, Duran FL, Santos LC, Hoexter MQ, Gentil AF, Canteras MM, Castro CC, Norén G, Greenberg BD, Rauch SL, Busatto GF, Miguel EC. Gamma ventral capsulotomy for treatment of resistant obsessive-compulsive disorder: a structural MRI pilot prospective study. Neurosci Lett. 2008 Dec 12;447(2-3):138-42. doi: 10.1016/j.neulet.2008.09.061. Epub 2008 Sep 27. — View Citation

Fodstad H, Strandman E, Karlsson B, West KA. Treatment of chronic obsessive compulsive states with stereotactic anterior capsulotomy or cingulotomy. Acta Neurochir (Wien). 1982;62(1-2):1-23. — View Citation

Frighetto L, Bizzi J, Annes RD, Silva Rdos S, Oppitz P. Stereotactic radiosurgery for movement disorders. Surg Neurol Int. 2012;3(Suppl 1):S10-6. doi: 10.4103/2152-7806.91605. Epub 2012 Jan 14. — View Citation

Frighetto L, De Salles A, Wallace R, Ford J, Selch M, Cabatan-Awang C, Solberg T. Linear accelerator thalamotomy. Surg Neurol. 2004 Aug;62(2):106-13; discussion 113-4. — View Citation

Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Heninger GR, Charney DS. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry. 1989 Nov;46(11):1012-6. — View Citation

Guy W, Wilson WH, Brooking B, Manov G, Fjetland O. Reliability and validity of SAFTEE: preliminar analyses. Psychopharmacol Bull. 1986;22(2):397-401. — View Citation

Hou J, Wu W, Lin Y, Wang J, Zhou D, Guo J, Gu S, He M, Ahmed S, Hu J, Qu W, Li H. Localization of cerebral functional deficits in patients with obsessive-compulsive disorder: a resting-state fMRI study. J Affect Disord. 2012 May;138(3):313-21. doi: 10.1016/j.jad.2012.01.022. Epub 2012 Feb 12. — View Citation

Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677-736. Review. — View Citation

Jenike MA, Rauch SL. Managing the patient with treatment-resistant obsessive compulsive disorder: current strategies. J Clin Psychiatry. 1994 Mar;55 Suppl:11-7. Review. — View Citation

Kelly DH, Walter CJ, Sargant W. Modified leucotomy assessed by forearm blood flow and other measurements. Br J Psychiatry. 1966 Sep;112(490):871-81. — View Citation

KNIGHT G. THE ORBITAL CORTEX AS AN OBJECTIVE IN THE SURGICAL TREATMENT OF MENTAL ILLNESS. THE RESULTS OF 450 CASES OF OPEN OPERATION AND THE DEVELOPMENT OF THE STEREOTACTIC APPROACH. Br J Surg. 1964 Feb;51:114-24. — View Citation

Leckman JF, Riddle MA, Hardin MT, Ort SI, Swartz KL, Stevenson J, Cohen DJ. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry. 1989 Jul;28(4):566-73. — View Citation

Lévêque M, Carron R, Régis J. Radiosurgery for the treatment of psychiatric disorders: a review. World Neurosurg. 2013 Sep-Oct;80(3-4):S32.e1-9. doi: 10.1016/j.wneu.2013.07.004. Epub 2013 Jul 17. Review. — View Citation

Lippitz B, Mindus P, Meyerson BA, Kihlström L, Lindquist C. Obsessive compulsive disorder and the right hemisphere: topographic analysis of lesions after anterior capsulotomy performed with thermocoagulation. Acta Neurochir Suppl. 1997;68:61-3. — View Citation

Lopes AC, Greenberg BD, Canteras MM, Batistuzzo MC, Hoexter MQ, Gentil AF, Pereira CA, Joaquim MA, de Mathis ME, D'Alcante CC, Taub A, de Castro DG, Tokeshi L, Sampaio LA, Leite CC, Shavitt RG, Diniz JB, Busatto G, Norén G, Rasmussen SA, Miguel EC. Gamma ventral capsulotomy for obsessive-compulsive disorder: a randomized clinical trial. JAMA Psychiatry. 2014 Sep;71(9):1066-76. doi: 10.1001/jamapsychiatry.2014.1193. — View Citation

McDougle CJ, Goodman WK, Leckman JF, Lee NC, Heninger GR, Price LH. Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics. Arch Gen Psychiatry. 1994 Apr;51(4):302-8. — View Citation

Miguel EC, Coffey BJ, Baer L, Savage CR, Rauch SL, Jenike MA. Phenomenology of intentional repetitive behaviors in obsessive-compulsive disorder and Tourette's disorder. J Clin Psychiatry. 1995 Jun;56(6):246-55. — View Citation

Mindus P, Rasmussen SA, Lindquist C. Neurosurgical treatment for refractory obsessive-compulsive disorder: implications for understanding frontal lobe function. J Neuropsychiatry Clin Neurosci. 1994 Fall;6(4):467-77. Review. — View Citation

Myers JK, Weissman MM, Tischler GL, Holzer CE 3rd, Leaf PJ, Orvaschel H, Anthony JC, Boyd JH, Burke JD Jr, Kramer M, et al. Six-month prevalence of psychiatric disorders in three communities 1980 to 1982. Arch Gen Psychiatry. 1984 Oct;41(10):959-67. — View Citation

Okada K, Ota T, Iida J, Kishimoto N, Kishimoto T. Lower prefrontal activity in adults with obsessive-compulsive disorder as measured by near-infrared spectroscopy. Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jun 3;43:7-13. doi: 10.1016/j.pnpbp.2012.11.013. Epub 2012 Dec 5. — View Citation

Ota T, Iida J, Sawada M, Suehiro Y, Yamamuro K, Matsuura H, Tanaka S, Kishimoto N, Negoro H, Kishimoto T. Reduced prefrontal hemodynamic response in pediatric obsessive-compulsive disorder as measured by near-infrared spectroscopy. Child Psychiatry Hum Dev. 2013 Apr;44(2):265-77. doi: 10.1007/s10578-012-0323-0. — View Citation

Perse T. Obsessive-compulsive disorder: a treatment review. J Clin Psychiatry. 1988 Feb;49(2):48-55. Review. — View Citation

Rasmussen SA, Eisen JL. Treatment strategies for chronic and refractory obsessive-compulsive disorder. J Clin Psychiatry. 1997;58 Suppl 13:9-13. Review. — View Citation

Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD Jr, Regier DA. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry. 1984 Oct;41(10):949-58. — View Citation

Rylander G. [Experiments with gammacapsulotomy in anxiety and compulsive neuroses]. Lakartidningen. 1978 Feb 15;75(7):547-9. Swedish. — View Citation

Spiegel EA, Wycis HT, Marks M, Lee AJ. Stereotaxic Apparatus for Operations on the Human Brain. Science. 1947 Oct 10;106(2754):349-50. — View Citation

Steketee G. Disability and family burden in obsessive-compulsive disorder. Can J Psychiatry. 1997 Nov;42(9):919-28. Review. — View Citation

Wang Y, Mathews CA, Li Y, Lin Z, Xiao Z. Brain-derived neurotrophic factor (BDNF) plasma levels in drug-naïve OCD patients are lower than those in healthy people, but are not lower than those in drug-treated OCD patients. J Affect Disord. 2011 Sep;133(1-2):305-10. doi: 10.1016/j.jad.2011.04.002. Epub 2011 May 25. — View Citation

Ware JE Jr, Kosinski M, Bayliss MS, McHorney CA, Rogers WH, Raczek A. Comparison of methods for the scoring and statistical analysis of SF-36 health profile and summary measures: summary of results from the Medical Outcomes Study. Med Care. 1995 Apr;33(4 Suppl):AS264-79. — View Citation

* Note: There are 37 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in OCD symptoms	Application of Yale-Brown Obsessive-Compulsive Scale (Y-Bocs) scale	Every 3 months until 12 months
Secondary	Change in quality of life.	Application of "Medical Outcomes Study 36-Item Short-Form Health Survey" (SF-36) scale	Every 3 months until 12 months
Secondary	Change in brain-derived neurotrophic factor (BDNF) blood dosing	Serological blood tests	12 months
Secondary	Change in psychological tests	Application of: Mini Mental Modified (3MS) test; Wechsler of intelligence test; Stroop of colors test; Tracks tests A and B; Boston Naming Test (BNT); Wechsler Memory Scale Revised (WMS-R); Wisconsin (WCST) test; Brief Visual Memory Test (BVLT); Hopkins Verbal Learning Test (HBLT) test; Benton Line Orientation (BLO) test; Grooved Pegboard Test; Finger Tapping test; Complex figure of Rey test	12 months
Secondary	Side effects and complications	Application of "Systematic Assessment for Treatment Emergent Effects" (SAFTEE) Event List and Interview.	Every 3 months until 12 months
Secondary	Change in familial accommodation	Application of "Family Accommodation Scale for Obsessive-Compulsive Disorder" (FAS)	Every 3 months until 12 months
Secondary	Change in anxiety symptoms.	Application of "Beck Anxiety Inventory" (BAI) scale	Every 3 months until 12 months
Secondary	Change in depressive symptoms.	Application of "Beck Depression Inventory" (BDI) scale	Every 3 months until 12 months
Secondary	Change in near-infrared spectroscopy (NIRS) brain blood flow	During application of Stroop psychological test.	12 months
Secondary	Change in OCD symptoms by CPRS	Application of "Comprehensive Psychopathological Rating Scale" (CPRS)	Every 3 months
Secondary	Change in OCD symptoms by NIMH.	Application of "National Institute of Mental Health Global Obsessive-Compulsive Scale" (NIMH OCD Scale)	Every 3 months
Secondary	Change in Global Functioning	Application of "Global Assessment of Functioning Scale" (GAF)	Every 3 months until 12 months