Clinical Trial of Tolcapone for Cognition in Schizophrenia

NCT00044083 | Terminated Phase 2 Results

• 3 other identifiers: 02023902-M-0239NCT00044083
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate whether Tolcapone improves cognition in healthy volunteers as well as patients with schizophrenia. Talcapone is a drug that has been FDA approved for Attention Deficit Disorder and allegedly increase the amount of the neurotransmitter dopamine in the frontal cortex of the brain. ...

Conditions

Schizophrenia

Keywords

Catecholamines; Dopamine; Clinical Trial; fMRI; PFC; Vitamin B2; Riboflavin; Tolcapone; Placebo; Normal Volunteers; Schizophrenia; Healthy Volunteers; HV

Outcome Measures

Primary Outcomes (7)

• N-Back Task Performance

  Working Memory was measured in HVs and patients with schizophrenia after a 7-day treatment with Tolcapone or placebo in a double-blind, cross-over fashion. The working memory was quantified by taking the number of trials entered correctly divided by the total number of trials multiplied by 100. Values range from 0 to 100. Zero indicates the poorest performance while 100 indicates perfect performance.

  At end of treatment period (at 7th day for first intervention and at 21st day for second intervention)

• N-Back Task Activation Diagnosis Effect

  Activation beta values (N-Back vs. 0-Back) were extracted within the Main Effect of Diagnosis cluster around the peak (p \< 0.05 uncorrected) from the contrast maps in the Placebo condition. Lower beta values reflect more efficient processing in the DLPFC when performing working memory tasks.

  At end of treatment period (at 7th day for first intervention and at 21st day for second intervention)

• N-Back Task Activation Drug Effect

  Activation beta values (N-Back vs. 0-Back) extracted within the Main Effect of Drug cluster around the peak (p \< 0.05 uncorrected) from the contrast maps across both groups. Lower beta values reflect more efficient processing in the DLPFC when performing working memory tasks.

  At end of treatment period (at 7th day for first intervention and at 21st day for second intervention)

• N-Back Task Activation in DLPFC in Patients With Schizophrenia

  Activation Beta values (N-Back vs. 0-Back) extracted within the Effect of Drug cluster around the peak (p \< 0.05 uncorrected) from the contrast maps in patients with schizophrenia. Lower beta values reflect more efficient processing in the DLPFC when performing working memory tasks.

  At end of treatment period (at 7th day for first intervention and at 21st day for second intervention)

• N-Back Task Activation in Healthy Volunteers

  Activation Beta values (N-Back vs. 0-Back) extracted within the Effect of Drug cluster around the peak (p \< 0.05 uncorrected) from the contrast maps in Healthy Volunteers. Lower beta values reflect more efficient processing in the DLPFC when performing working memory tasks.

  At end of treatment period (at 7th day for first intervention and at 21st day for second intervention)

• N-Back Task Activation Genotype Effect in Healthy Volunteers

  Activation beta values (N-Back vs. 0-Back) extracted within the Effect of Genotype cluster around the peak (p \< 0.05 uncorrected) in right and left DLPFC from the contrast maps in Healthy Volunteers. Lower beta values reflect more efficient processing in the DLPFC when performing working memory tasks.

  At end of treatment period (at 7th day for first intervention and at 21st day for second intervention)

• N-Back Task Activation by Genotype in Patients With Schizophrenia

  Activation beta values (N-Back vs. 0-Back) extracted from DLPFC from the contrast maps in Patients with schizophrenia. Lower beta values reflect more efficient processing in the DLPFC when performing working memory tasks.

  At end of treatment period (at 7th day for first intervention and at 21st day for second intervention)

Secondary Outcomes (1)

• Positive and Negative Syndrome Scale

  At end of treatment period (at 7th day for first intervention and at 21st day for second intervention)

Study Arms (2)

Placebo Arm

PLACEBO COMPARATOR

Placebo one week

Other: Placebo

Tolcapone Arm

ACTIVE COMPARATOR

Tolcapone one week

Drug: Tolcapone

Interventions

Placebo OTHER

Placebo: One capsule 3 times a day from Day 1 to Day 7

Placebo Arm

Tolcapone DRUG

Tolcapone: One capsule 3 times a day from Day 1 to Day 7

Also known as: Tasmar

Tolcapone Arm

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Prior participation under NIH protocol number 95-M-0150, or new normal volunteers or schizophrenic patients that meet criteria for NIH protocol number 95-M-0150 (NCT00001486).
• No Axis I or Axis II diagnosis in normal volunteers.
• Age range: 18-50 years.

You may not qualify if:

• Normal volunteers with an Axis I or Axis II disorder obtained either from prior SCID interview in Protocol 95-M-0150 or through a screening interview will be excluded.
• Subjects with a history of cardiovascular disease, liver disease and other medical illnesses, and untreated or uncontrolled hypertension will be excluded. An electrocardiogram, blood pressure, pulse rate and metabolic panel including LFTs will be checked on all subjects prior to participation in the study. Individuals with persistent tardive dyskinesia or abnormal LFTs, or individuals with significant history of alcoholism or liver enzyme elevation will be excluded from the study.
• Schizophrenic patients taking clozapine, a COMT inhibitor, any illicit drugs of abuse, or MAO inhibitors will be excluded.
• Normal control subjects taking any medications other than occasional NSAI will be excluded.
• Pregnant women. Women of childbearing potential will undergo a urine pregnancy test the day the study initiates and screened by history for the possibility of pregnancy.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Aksoy S, Klener J, Weinshilboum RM. Catechol O-methyltransferase pharmacogenetics: photoaffinity labelling and western blot analysis of human liver samples. Pharmacogenetics. 1993 Apr;3(2):116-22. doi: 10.1097/00008571-199304000-00008.

  PMID: 8518836 BACKGROUND

• Andreasen NC, Arndt S, Cizadlo T, O'Leary DS, Watkins GL, Ponto LL, Hichwa RD. Sample size and statistical power in [15O]H2O studies of human cognition. J Cereb Blood Flow Metab. 1996 Sep;16(5):804-16. doi: 10.1097/00004647-199609000-00005.

  PMID: 8784225 BACKGROUND

• Arnsten AF. Catecholamine regulation of the prefrontal cortex. J Psychopharmacol. 1997;11(2):151-62. doi: 10.1177/026988119701100208.

  PMID: 9208378 BACKGROUND

• Magalona SC, Rasetti R, Chen J, Chen Q, Gold I, Decot H, Callicott JH, Berman KF, Apud JA, Weinberger DR, Mattay VS. Effect of tolcapone on brain activity during a variable attentional control task: a double-blind, placebo-controlled, counter-balanced trial in healthy volunteers. CNS Drugs. 2013 Aug;27(8):663-73. doi: 10.1007/s40263-013-0082-x.

  PMID: 23794107 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Schizophrenia

Interventions

Tolcapone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

There was an early termination due to a request from the NIMH leadership to assess if was justifiable to continue when considering costs of this research and needs to assess resources to develop new protocols for the Branch

Results Point of Contact

• Title: Jose A. Apud
• Organization: Office of the Clinical Director-NIMH-NIH-HHS

apudj@mail.nih.gov

3015946561

Study Officials

• Jose A Apud, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: August 16, 2002
• First Posted: August 19, 2002
• Study Start: August 1, 2002
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 27, 2018
• Results First Posted: July 17, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)