Evaluate the Effects of Tolcapone on Cognitive and Behavioral Dysfunction in Patients With BI and NCD

NCT02652598 | Unknown Phase 2 DMC

• 1 other identifier: 805704
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The experimental design is an open-label two-week trial of tolcapone to evaluate which clinical domains are affected by tolcapone treatment and to identify "responders" to tolcapone treatment in the two subject groups (BI and NCD)

Conditions

Brain Injuries, Traumatic; Neurocognitive Disorders; Brain Injuries

Outcome Measures

Primary Outcomes (1)

• Change from Baseline Clinical Global Impression Scale (CGI) to two weeks after medication administration

  Up to 2 weeks

Secondary Outcomes (2)

• Change from Baseline TBI-QoL to two weeks after medication administration

  Up to 2 weeks

• Change from Baseline NIH Toolbox Cognition Battery to two weeks after medication administration

  Up to 2 weeks

Study Arms (1)

Open-Label

EXPERIMENTAL

Each patient will receive a two-week specified dosing amount of tolcapone (100mg TID on Day 1; 200mg TID on Days 2-14). The patient will be instructed to take the study drug three times daily. Tolcapone will be tapered after Day 14 to avoid potential withdrawal reactions.

Drug: Tolcapone

Interventions

Tolcapone DRUG

Also known as: Tasmar

Open-Label

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70
• Diagnosis of mild, moderate, or severe TBI, or history of ABI with classification to be made based on parameters at the time of the index event or acquired brain injury.
• Index event resulting in Traumatic or Acquired Head Injury occurred \>12 months prior to trial initiation
• A current or former patient at the clinics of the Sheppard Pratt Neuropsychiatry Program or another Sheppard Pratt outpatient clinic with medical documentation of TBI or ABI
• Proficient in the English language
• Available to come to Sheppard Pratt Towson for the baseline evaluation and testing and for the duration of the protocol
• Stable neurological and psychiatric symptomatology for 2 months prior to trial initiation as determined by the referring Sheppard Pratt physician.
• Stable medication dose and regimen for 2 months
• Age 60-75
• NCD diagnosed by a Sheppard Pratt physician, per DSM-5
• No abnormalities on other serum tests to rule out other cause of cognitive impairment: TSH, B12, CBC, Chemistry screen, and RPR.
• Recent structural neuroimaging (within 1 year or since the time of the onset of cognitive complaint)-noncontrast head CT or MRI-to rule out any gross lesion inconsistent with the diagnosis of MCI (e.g. subdural hematoma, normal pressure hydrocephalus, demyelinating lesion, infarct, or mass lesion)
• Proficient in the English language
• A current or former patient at the clinics of the Sheppard Pratt Neuropsychiatry Program or another Sheppard Pratt outpatient clinic with medical documentation of NCD
• Available to come to Sheppard Pratt Towson for the baseline evaluation and testing and for the duration of the protocol

You may not qualify if:

• History of, or active, liver disease or abnormal liver function tests--if the patient currently has elevated Alanine Transaminase (ALT) or Aspartate Transaminase (AST) levels that exceed 2 times the upper limit of normal \[Normal Reference Ranges ALT (Male: 4-40 IU/L, Female: 4-40 IU/L), AST (Male: 4-31 IU/L, Female: 4-37 IU/L) or the ratio of AST:ALT has exceeded 2:1
• Active alcohol use disorder, as defined by DSM-5, of any severity mild, moderate, or severe
• History of, or active, cardiovascular disease defined as: coronary heart disease, manifested by myocardial infarction, angina pectoris, or heart failure
• Uncontrolled hypo-or hypertension based on Joint National Committee criteria (JNC7) Hypotension: Systolic\<90mmHg or diastolic\<60mmHg Hypertension: Systolic \>140mmHg or diastolic\>90 mmHg)
• History of extra-pyramidal symptoms (e.g. tardive dyskinesia, neuroleptic malignant syndrome, or QT prolongation) while on a first-generation anti-psychotic
• Active illicit substance use, resulting in a substance use disorder as defined by DSM-5, of any severity mild, moderate, or severe
• Patient is currently taking tolcapone or any of the following medications that can interact with tolcapone resulting in an adverse events: another COMT inhibitor, benserazide, α-methyldopa, dobutamine, apomorphine, isoproterenol, clozapine, MAO inhibitor
• Known allergy or serious adverse reaction to tolcapone
• Participated in any investigational drug trial in the past 30 days.
• Pregnant or planning to become pregnant during the study period
• Breastfeeding or planning to breastfeed during the study period.
• Presence of pre-morbid/pre-TBI cognitive impairment or behavioral dysfunction, as per informant or medical documentation

Sponsors & Collaborators

• Sheppard Pratt Health System: lead
• Lieber Institute for Brain Development (LIBD): collaborator

Study Sites (1)

Sheppard Pratt Health System

Baltimore, Maryland, 21204, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Neurocognitive Disorders; Brain Injuries

Interventions

Tolcapone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Robert J Schloesser, MD

  Sheppard Pratt Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Director of Sheppard Pratt-Lieber Research Institute, Inc.

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 12, 2016
• Study Start: November 1, 2015
• Primary Completion: January 1, 2020
• Last Updated: January 19, 2017

Record last verified: 2017-01

Locations

US (1)