TTI-0102 for Veterans With TBI

NCT04262895 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: N3323-PI21RX003323-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Traumatic brain injury (TBI) is a signature wound of the recent wars. How chronic TBI symptoms develop after a mild brain injury is not fully understood, but it is now thought that injury results in damage that reduces brain energy production, increases inflammation, and results in a leaky blood-brain barrier. Difficulties in daily function may persist in areas such as thinking (e.g., attention, learning, memory, planning, and problem-solving), pain (e.g., headache) and behavior (e.g., sleep, posttraumatic stress disorder, depression). No medications for TBI have been developed, so evidence-based cognitive rehabilitation interventions such as Compensatory Cognitive Training (CCT) are the mainstay of treatment. The investigators are proposing to study a medication, TTI-0102, that shows anti-inflammatory activity, as a potential adjunct treatment with CCT for Veterans with TBI-related symptoms. The investigators plan to first determine the best dose of TTI-0102 to use, and then to conduct a pilot study to test the feasibility and acceptability of combining TTI-0102 with CCT in Veterans with mild to moderate TBI and PTSD.

Conditions

Mild to Moderate TBI; Posttraumatic Stress Disorder

Keywords

cognition; neurobehavioral symptoms; psychiatric symptoms

Outcome Measures

Primary Outcomes (1)

• Objective cognition

  Mean z-score of objective cognitive measures (Wechsler Adult Intelligence Scale-4th Edition Digit Span, WAIS-IV Coding, Hopkins Verbal Learning Test-Revised, Brief Visuospatial Memory Test-Revised, Delis-Kaplan Executive Function System Trails, D-KEFS Color-Word Interference, D-KEFS Verbal Fluency)

  Change from 0 to 12 weeks

Secondary Outcomes (10)

• Subjective cognition

  Change from 0 to 12 weeks

• Neuropsychiatric symptoms

  Change from 0 to 12 weeks

• high-sensitive C-reactive protein

  Change from 0 to 12 weeks

• interleukin-6

  change from 0 to 12 weeks

• brain-derived neurotrophic factor

  change from 0 to 12 weeks

Study Arms (3)

TTI-0102 2 mg/day

EXPERIMENTAL

TTI-0102 2 mg/day

Drug: TTI-0102

TTI-0102 4 mg/day

EXPERIMENTAL

TTI-0102 4 mg/day

Drug: TTI-0102

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

TTI-0102 DRUG

TTI-0102 is a cysteamine precursor.

TTI-0102 2 mg/day; TTI-0102 4 mg/day

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Veteran receiving care at the VA San Diego Healthcare system
• age 18-65
• history of mild to moderate TBI (loss of consciousness \<24 hours; posttraumatic amnesia \<7 days)
• documented impairment (\>1 standard deviation below the mean) in at least one neuropsychological domain as determined by valid clinical neuropsychological testing using at least one performance validity test, i.e.:
• attention
• processing speed
• working memory
• learning, memory
• executive functioning
• DSM-5 diagnosis of PTSD based on the Clinician-Administered PTSD Scale

You may not qualify if:

• current alcohol and/or substance abuse or dependence
• high risk for homicide or suicide
• evidence of a significant uncontrolled/unstable medical illness or clinically significant surgery
• laboratory values that are significantly outside normal limits
• history of intolerance or hypersensitivity to cysteamine or penicillamine
• current participation in other intervention studies
• pregnant or intending to become pregnant in the next 3 months

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

cysteamine-pantetheine disulfide

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Elizabeth W. Twamley, PhD

  VA San Diego Healthcare System, San Diego, CA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Doses of drug and placebo will be prepared in identical sachets, with group assignment known only to the research pharmacist.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: In Phase 1, the investigators will determine whether TTI-0102 2 mg/day or 4 mg/day is more tolerated and/or more effective compared with placebo in Veterans with mild to moderate TBI and PTSD. In Phase 2, the investigators will determine the feasibility and acceptability of trial procedures involving TTI-0102 (dose determined in Phase 1) vs placebo in Veteran participants receiving Compensatory Cognitive Training.

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 10, 2020
• Study Start: October 1, 2021
• Primary Completion: October 15, 2021
• Study Completion: October 15, 2021
• Last Updated: October 26, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Following study completion, indefinitely.
• Access Criteria: Upon request.

Locations

US (1)