Back to results

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

Primary Purpose

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

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Tolcapone 200 MG

Placebo

About this trial

This is an interventional treatment trial for Brain Injuries focused on measuring Brain Injury, Traumatic Brain Injury, Acquired Brain Injury, Cognition, Neuropsychiatric Symptopms, COMT

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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 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)

Exclusion Criteria:

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

Sites / Locations

Sheppard Pratt Health SystemRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Study Period 1

Study Period 2

Arm Description

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

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

Outcomes

Primary Outcome Measures

NIH Toolbox Fluid Cognitive Battery

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

Secondary Outcome Measures

TBI Quality-of-Life Measurement System

A patient reported outcome measure assessing physical, emotional, cognitive and social functioning. Quality of Life Measure is a computer adaptive questionnaire.

Frontal Systems Behavior Scale

A patient reported outcome measure, and proxy reported outcome measure, assessing neuropsychiatric symptoms associated with prefrontal cortical dysfunction

Full Information

NCT ID

NCT03273062

First Posted

August 31, 2017

Last Updated

September 1, 2017

Sponsor

Sheppard Pratt Health System

Collaborators

Lieber Institute for Brain Development

1. Study Identification

Unique Protocol Identification Number

NCT03273062

Brief Title

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

Official Title

A Double-blind, Placebo-controlled Clinical Trial to Evaluate the Effects of Catechol-O-Methyltransferase (COMT) Inhibition on Cognition and Neuropsychiatric Symptoms in Patients With a History of Acquired Brain Injuries

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Unknown status

Study Start Date

July 20, 2017 (Actual)

Primary Completion Date

July 20, 2018 (Anticipated)

Study Completion Date

July 20, 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sheppard Pratt Health System

Collaborators

Lieber Institute for Brain Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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).

Detailed Description

The proposed study 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). The outcome measures utilized in this study were chosen based on the available data from the currently ongoing open-label clinical trial. The proposed study will utilize the same study medication at the same dose and frequency. In addition, the length of administration of study medication (two weeks) is identical. In the proposed 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 be evaluated through participant and proxy report. The investigators are planning to randomize a total of 12 patients with BI. The cross-over design requires two 2-week long study periods during which the participant receives either Tolcapone two 100mg capsules three times a day (total of 600mg/day) or placebo. Participants will be randomly assigned to two sequence groups either starting with Tolcapone treatment (T-P group) or placebo (P-T group). Investigators and participants will be blind to the study group assignment and hence blind to the treatment (Tolcapone vs. placebo) that subjects receive at a given time. The study periods are separated by a "washout period" that is at least two weeks and maximally 4 weeks long to reduce the potential for carryover effects. Patient reported outcomes will be obtained a total of four times, twice prior to the start of each respective study period (Pre-Study Period Visits I & II) as well as at the end of each study period (Outcome Measures Visits I & II). Cognitive outcome measures will be obtained twice throughout the study, at the end of each respective study period (Outcome Measures Visits I & II).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Model Description

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

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

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.

Allocation

Randomized

Enrollment

16 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Study Period 1

Arm Type

Active Comparator

Arm Description

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

Arm Title

Study Period 2

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Tolcapone 200 MG

Other Intervention Name(s)

Tasmar

Intervention Description

Tolcapone 200 MG TID

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

NIH Toolbox Fluid Cognitive Battery

Description

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

Time Frame

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

Secondary Outcome Measure Information:

Title

TBI Quality-of-Life Measurement System

Description

A patient reported outcome measure assessing physical, emotional, cognitive and social functioning. Quality of Life Measure is a computer adaptive questionnaire.

Time Frame

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).

Title

Frontal Systems Behavior Scale

Description

A patient reported outcome measure, and proxy reported outcome measure, assessing neuropsychiatric symptoms associated with prefrontal cortical dysfunction

Time Frame

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).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 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) Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Robert J Schloesser, MD

Phone

410-938-4610

rschloesser@sheppardpratt.org

First Name & Middle Initial & Last Name or Official Title & Degree

Emily A Berich, BS

Phone

410-938-4610

eberich@sheppardpratt.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert J Schloesser, MD

Organizational Affiliation

Sheppard Pratt Health System

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sheppard Pratt Health System

City

Towson

State/Province

Maryland

ZIP/Postal Code

21204

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Robert J Schloesser, MD

Phone

410-938-4666

rscloesser@sheppardpratt.org

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

We'll reach out to this number within 24 hrs