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

NCT03273062 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: 1087860-3
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a follow-up study for an ongoing open label trial conducted by the Sheppard Pratt-Lieber Research Institute utilizing the catechol-O-methyl-transferase (COMT) inhibitor Tolcapone to evaluate its effects on cognition and neuropsychiatric symptoms in patients with brain injuries (BI). In this study, investigators will conduct a double-blind, placebo-controlled clinical trial utilizing a crossover design to study the effects of two weeks of Tolcapone 200mg administered three times a day (total of 600mg/day) on cognitive performance. Physical, emotional, cognitive and social functioning will also be evaluated through participant and proxy report. The investigators are planning to randomize a total of 12 patients with a history of acquired brain injury (BI).

Conditions

Brain Injuries; Brain Injuries, Traumatic; Brain Injury, Chronic

Keywords

Brain Injury; Traumatic Brain Injury; Acquired Brain Injury; Cognition; Neuropsychiatric Symptopms; COMT

Outcome Measures

Primary Outcomes (1)

• NIH Toolbox Fluid Cognitive Battery

  This battery is a measure of cognitive performance derived from a battery of five cognitive assessments.

  Administered on the 14th day of Tolcapone or Placebo treatment (i.e. during each Outcome Measures Visit).

Secondary Outcomes (2)

• TBI Quality-of-Life Measurement System

  Administered prior to the start of Tolcapone oe Placebo treatment (i.e. during each Pre-Study Visit) and on the 14th day of Tolcapone or Placebo treatment (i.e. during each Outcome Measures Visit).

• Frontal Systems Behavior Scale

  Administered prior to the start of Tolcapone oe Placebo treatment (i.e. during each Pre-Study Visit) and on the 14th day of Tolcapone or Placebo treatment (i.e. during each Outcome Measures Visit).

Study Arms (2)

Study Period 1

ACTIVE COMPARATOR

15 days of Tolcapone 200mg TID OR Placebo Comparator 15 days of Placebo pill TID

Drug: Tolcapone 200 MG; Other: Placebo

Study Period 2

PLACEBO COMPARATOR

15 days of Placebo pill TID OR Active Comparator 15 days of Tolcapone 200mg TID

Drug: Tolcapone 200 MG; Other: Placebo

Interventions

Tolcapone 200 MG DRUG

Tolcapone 200 MG TID

Also known as: Tasmar

Study Period 1; Study Period 2

Placebo OTHER

Placebo, TID Placebo will be in capsules that are identical in appearance to intervention drug, Tolcapone.

Study Period 1; Study Period 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capacity for written informed consent
• Ages 18-70 years, inclusive
• Diagnosis of a BI including mild, moderate, or severe TBI, or other acquired BI and post-BI development of neuropsychiatric complaints.
• Index event resulting in Traumatic or Acquired Brain 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 BI
• 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 two months prior to trial initiation as determined by the referring Sheppard Pratt physician.
• Stable medication dose and regimen for two months prior to trial initiation (based on a review of medical chart)

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
• Uncontrolled hypo-or hypertension based on Joint National Committee criteria (JNC7) Hypotension: Systolic \<90mmHg or diastolic \<60mmHg Hypertension: Systolic \>140mmHg or diastolic \>90 mmHg)
• Active alcohol use disorder, as defined by DSM-5, of any severity mild, moderate, or severe
• 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 event: 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 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

Sponsors & Collaborators

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

Study Sites (1)

Sheppard Pratt Health System

Towson, Maryland, 21204, United States

RECRUITING

MeSH Terms

Conditions

Brain Injuries; Brain Injuries, Traumatic; Brain Injury, Chronic

Interventions

Tolcapone

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Brain Damage, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

Central Study Contacts

Robert J Schloesser, MD

CONTACT

410-938-4610; rschloesser@sheppardpratt.org

Emily A Berich, BS

CONTACT

410-938-4610; eberich@sheppardpratt.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participant, respective care provider, as well as the investigator and research coordinator ("outcomes assessor") will all be blind to the order of placebo or medication (Tolcapone) administration in this two-arm, crossover study.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Director, Sheppard Pratt-Lieber Research Institute, Inc.

Model Details: Interventional clinical trial with a double-blind, randomized placebo-controlled crossover design

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: September 6, 2017
• Study Start: July 20, 2017
• Primary Completion: July 20, 2018
• Study Completion: July 20, 2018
• Last Updated: September 6, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)