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

• Status: Unknown status
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sheppard Pratt Health System
• Collaborator: Lieber Institute for Brain Development (LIBD)
• Treatments: Tolcapone

Criteria

TBI and ABI Patients Inclusion Criteria

• 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

NCD Patients Inclusion Criteria

• 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

• Stable neurological and psychiatric symptomatology for 2 months prior to trial initiation as determined by the impression of the referring Sheppard Pratt physician.

• Stable medication dose and regimen for 2 months

Exclusion Criteria for All Patients:

• 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.

Other Exclusion Criteria for TBI Patients

• Presence of pre-morbid/pre-TBI cognitive impairment or behavioral dysfunction, as per informant or medical documentation