A Trial Evaluating Effects of COMT Inhibition in Patients With Acquired Brain Injury

Inclusion Criteria:

• Capacity for written informed consent

• Ages 18-70 years, inclusive

• Diagnosis of a BI including mild, moderate, or severe TBI, or other acquired BI andpost-BI development of neuropsychiatric complaints.

• Index event resulting in Traumatic or Acquired Brain Injury occurred >12 months priorto trial initiation

• A current or former patient at the clinics of the Sheppard Pratt NeuropsychiatryProgram or another Sheppard Pratt outpatient clinic with medical documentation of BI

• Proficient in the English language

• Available to come to Sheppard Pratt Towson for the baseline evaluation and testing andfor the duration of the protocol

• Stable neurological and psychiatric symptomatology for two months prior to trialinitiation as determined by the referring Sheppard Pratt physician.

• Stable medication dose and regimen for two months prior to trial initiation (based ona review of medical chart)

Exclusion Criteria:

• History of, or active, liver disease or abnormal liver function tests-if the patientcurrently 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 theratio of AST: ALT has exceeded 2:1

• Uncontrolled hypo-or hypertension based on Joint National Committee criteria (JNC7)Hypotension: Systolic <90mmHg or diastolic <60mmHg Hypertension: Systolic >140mmHg ordiastolic >90 mmHg)

• Active alcohol use disorder, as defined by DSM-5, of any severity mild, moderate, orsevere

• Active illicit substance use, resulting in a substance use disorder as defined byDSM-5, of any severity mild, moderate, or severe

• Patient is currently taking Tolcapone or any of the following medications that caninteract with Tolcapone resulting in an adverse event: another COMT inhibitor,benserazide, α-methyldopa, Dobutamine, Apomorphine, Isoproterenol, Clozapine, MAOinhibitor

• Known allergy or serious adverse reaction to Tolcapone

• Participated in any investigational drug trial within 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 severe pre-morbid/pre-BI cognitive impairment or behavioral dysfunction,as per informant or medical documentation