Tolcapone in Obsessive Compulsive Disorder

NCT03348930 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 17-1379
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study will consist of a 5-week double-blind cross-over study trial of tolcapone in 20 people (ages 18-65). The study will be divided into an initial 2 week phase and a second 2 week phase, with one of the 2 week phases consisting of active treatment with tolcapone, and the other 2 week phase consisting of inactive placebo treatment. There will be a one-week wash-out phase between the 2-week treatment phases. Participants will be randomized to receive either tolcapone or placebo during the first 2 week phase on a 1:1 basis. This blinding will be maintained by the IDS pharmacy at the University of Chicago.

Conditions

Obsessive-Compulsive Disorder

Outcome Measures

Primary Outcomes (1)

• Yale Brown Obsessive Compulsive Scale (Y-BOCS)

  The entire study for the subject will last 5 weeks. Every 2 weeks and after the one week washout period the subject will take the YBOCS. The change in scores from baseline to after 5 weeks will be assessed. The scale itself assesses severity of OCD symptoms. The YBOCS scale ranges from 0 to 40, with 0 being no symptoms and 40 being severe.

  2 weeks (start of study to washout period OR two weeks following washout period)

Secondary Outcomes (4)

• Clinical Global Impression- Severity and Improvement (CGI)

  2 weeks (start of study to washout period OR two weeks following washout period)

• Sheehan Disability Scale (SDS)

  2 weeks (start of study to washout period OR two weeks following washout period)

• Hamilton Anxiety Rating Scale (HAM-A)

  2 weeks (start of study to washout period OR two weeks following washout period)

• Hamilton Depression Rating Scale (HAM-D)

  2 weeks (start of study to washout period OR two weeks following washout period)

Study Arms (2)

Tolcapone

EXPERIMENTAL

Each subject will have a 4 week treatment phase with Tolcapone

Drug: Tolcapone 200 MG

Placebo

PLACEBO COMPARATOR

4 week placebo phase before or after Tolcapone phase depending on randomization.

Drug: Tolcapone 200 MG

Interventions

Tolcapone 200 MG DRUG

All eligible study subjects will go through a 2-week treatment phase during which they will begin tolcapone at 100mg twice a day.

Also known as: No other names

Placebo; Tolcapone

Eligibility Criteria

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

You may qualify if:

• Males and females age 18-65;
• Diagnosis of current OCD based on DSM-5 criteria and confirmed using the clinician-administered Structured Clinical Interview for DSM-5 (SCID);
• Able and willing to provide written consent for participation.

You may not qualify if:

• Unstable medical illness, including liver disease, as determined by the investigator;
• History of seizures;
• Clinically significant suicidality (defined by the Columbia Suicide Severity Rating Scale);
• Baseline score of ≥17 on the Hamilton Depression Rating Scale (17-item HDRS);
• Lifetime history of bipolar disorder type I or II, schizophrenia, autism, any psychotic disorder, or any substance use disorder;
• Initiation of psychotherapy or behavior therapy within 3 months prior to study baseline;
• Previous treatment with tolcapone;
• Any history of psychiatric hospitalization in the past year;
• Currently pregnant (confirmed by urine pregnancy test)

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (29)

• Saxena S, Rauch SL. Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr Clin North Am. 2000 Sep;23(3):563-86. doi: 10.1016/s0193-953x(05)70181-7.

  PMID: 10986728 BACKGROUND

• Baxter LR Jr, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE. Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. Arch Gen Psychiatry. 1987 Mar;44(3):211-8. doi: 10.1001/archpsyc.1987.01800150017003.

  PMID: 3493749 BACKGROUND

• Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012 Jan;16(1):43-51. doi: 10.1016/j.tics.2011.11.003. Epub 2011 Dec 2.

  PMID: 22138231 BACKGROUND

• Graybiel AM, Rauch SL. Toward a neurobiology of obsessive-compulsive disorder. Neuron. 2000 Nov;28(2):343-7. doi: 10.1016/s0896-6273(00)00113-6. No abstract available.

  PMID: 11144344 BACKGROUND

• Piras F, Piras F, Caltagirone C, Spalletta G. Brain circuitries of obsessive compulsive disorder: a systematic review and meta-analysis of diffusion tensor imaging studies. Neurosci Biobehav Rev. 2013 Dec;37(10 Pt 2):2856-77. doi: 10.1016/j.neubiorev.2013.10.008. Epub 2013 Oct 28.

  PMID: 24177038 BACKGROUND

• Menzies L, Achard S, Chamberlain SR, Fineberg N, Chen CH, del Campo N, Sahakian BJ, Robbins TW, Bullmore E. Neurocognitive endophenotypes of obsessive-compulsive disorder. Brain. 2007 Dec;130(Pt 12):3223-36. doi: 10.1093/brain/awm205. Epub 2007 Sep 13.

  PMID: 17855376 BACKGROUND

• Chamberlain SR, Menzies L, Hampshire A, Suckling J, Fineberg NA, del Campo N, Aitken M, Craig K, Owen AM, Bullmore ET, Robbins TW, Sahakian BJ. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science. 2008 Jul 18;321(5887):421-2. doi: 10.1126/science.1154433.

  PMID: 18635808 BACKGROUND

• Skoog G, Skoog I. A 40-year follow-up of patients with obsessive-compulsive disorder [see commetns]. Arch Gen Psychiatry. 1999 Feb;56(2):121-7. doi: 10.1001/archpsyc.56.2.121.

  PMID: 10025435 BACKGROUND

• Mancebo MC, Eisen JL, Pinto A, Greenberg BD, Dyck IR, Rasmussen SA. The brown longitudinal obsessive compulsive study: treatments received and patient impressions of improvement. J Clin Psychiatry. 2006 Nov;67(11):1713-20. doi: 10.4088/jcp.v67n1107.

  PMID: 17196050 BACKGROUND

• Blanco C, Olfson M, Stein DJ, Simpson HB, Gameroff MJ, Narrow WH. Treatment of obsessive-compulsive disorder by U.S. psychiatrists. J Clin Psychiatry. 2006 Jun;67(6):946-51. doi: 10.4088/jcp.v67n0611.

  PMID: 16848654 BACKGROUND

• Grant JE. Clinical practice: Obsessive-compulsive disorder. N Engl J Med. 2014 Aug 14;371(7):646-53. doi: 10.1056/NEJMcp1402176.

  PMID: 25119610 BACKGROUND

• Tunbridge EM, Bannerman DM, Sharp T, Harrison PJ. Catechol-o-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex. J Neurosci. 2004 Jun 9;24(23):5331-5. doi: 10.1523/JNEUROSCI.1124-04.2004.

  PMID: 15190105 BACKGROUND

• Mier D, Kirsch P, Meyer-Lindenberg A. Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis. Mol Psychiatry. 2010 Sep;15(9):918-27. doi: 10.1038/mp.2009.36. Epub 2009 May 5.

  PMID: 19417742 BACKGROUND

• Apud JA, Mattay V, Chen J, Kolachana BS, Callicott JH, Rasetti R, Alce G, Iudicello JE, Akbar N, Egan MF, Goldberg TE, Weinberger DR. Tolcapone improves cognition and cortical information processing in normal human subjects. Neuropsychopharmacology. 2007 May;32(5):1011-20. doi: 10.1038/sj.npp.1301227. Epub 2006 Oct 25.

  PMID: 17063156 BACKGROUND

• Servan-Schreiber D, Printz H, Cohen JD. A network model of catecholamine effects: gain, signal-to-noise ratio, and behavior. Science. 1990 Aug 24;249(4971):892-5. doi: 10.1126/science.2392679.

  PMID: 2392679 BACKGROUND

• Seamans JK, Yang CR. The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Prog Neurobiol. 2004 Sep;74(1):1-58. doi: 10.1016/j.pneurobio.2004.05.006.

  PMID: 15381316 BACKGROUND

• Malhotra AK, Kestler LJ, Mazzanti C, Bates JA, Goldberg T, Goldman D. A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition. Am J Psychiatry. 2002 Apr;159(4):652-4. doi: 10.1176/appi.ajp.159.4.652.

  PMID: 11925305 BACKGROUND

• Roussos P, Giakoumaki SG, Pavlakis S, Bitsios P. Planning, decision-making and the COMT rs4818 polymorphism in healthy males. Neuropsychologia. 2008 Jan 31;46(2):757-63. doi: 10.1016/j.neuropsychologia.2007.10.009. Epub 2007 Oct 22.

  PMID: 18037454 BACKGROUND

• Bitsios P, Roussos P. Tolcapone, COMT polymorphisms and pharmacogenomic treatment of schizophrenia. Pharmacogenomics. 2011 Apr;12(4):559-66. doi: 10.2217/pgs.10.206.

  PMID: 21521027 BACKGROUND

• Roussos P, Giakoumaki SG, Bitsios P. Tolcapone effects on gating, working memory, and mood interact with the synonymous catechol-O-methyltransferase rs4818c/g polymorphism. Biol Psychiatry. 2009 Dec 1;66(11):997-1004. doi: 10.1016/j.biopsych.2009.07.008. Epub 2009 Aug 22.

  PMID: 19699472 BACKGROUND

• Forsberg M, Lehtonen M, Heikkinen M, Savolainen J, Jarvinen T, Mannisto PT. Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat. J Pharmacol Exp Ther. 2003 Feb;304(2):498-506. doi: 10.1124/jpet.102.042846.

  PMID: 12538800 BACKGROUND

• Blum K, Chen TJ, Meshkin B, Waite RL, Downs BW, Blum SH, Mengucci JF, Arcuri V, Braverman ER, Palomo T. Manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is dependent upon gene polymorphisms: a hypothesis. Med Hypotheses. 2007;69(5):1054-60. doi: 10.1016/j.mehy.2006.12.062. Epub 2007 Apr 30.

  PMID: 17467918 BACKGROUND

• Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.

  PMID: 9881538 BACKGROUND

• Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry. 1989 Nov;46(11):1006-11. doi: 10.1001/archpsyc.1989.01810110048007.

  PMID: 2684084 BACKGROUND

• Olanow CW, Watkins PB. Tolcapone: an efficacy and safety review (2007). Clin Neuropharmacol. 2007 Sep-Oct;30(5):287-94. doi: 10.1097/wnf.0b013e318038d2b6.

  PMID: 17909307 BACKGROUND

• HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.

  PMID: 14399272 BACKGROUND

• HAMILTON M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50-5. doi: 10.1111/j.2044-8341.1959.tb00467.x. No abstract available.

  PMID: 13638508 BACKGROUND

• Sheehan DV. (1983). The Anxiety Disease. New York: Scribner's.

  BACKGROUND

• Guy W (1976). ECDEU Assessment Manual for Psychopharmacology. US Dept Health, Education and Welfare publication (ADM) 76-338. Rockville, MD: National Institute of Mental Health, 218-222.

  BACKGROUND

MeSH Terms

Conditions

Obsessive-Compulsive Disorder

Interventions

Tolcapone

Condition Hierarchy (Ancestors)

Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitrophenols; Phenols; Ketones; Nitro Compounds

Results Point of Contact

• Title: Dr. Jon Grant
• Organization: University of Chicago

jgrant4@bsd.uchicago.edu

7738341325

Study Officials

• Jon E Grant, JD,MD,MPH

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2017
• First Posted: November 21, 2017
• Study Start: March 20, 2018
• Primary Completion: December 14, 2020
• Study Completion: December 14, 2020
• Last Updated: April 7, 2022
• Results First Posted: April 7, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)