MedDataX Logo

TTI-0102 for Veterans With TBI

NCT ID: NCT04262895

Last Updated: 2021-10-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1/PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-01

Study Completion Date

2021-10-15

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Approximately 12-23% of returning service members report a history of traumatic brain injury, mostly mild (mTBI). Post-concussive symptoms such as memory problems, irritability, and difficulty concentrating are common after TBI and may become chronic, interfering with successful return to duty or civilian reintegration, reducing quality of life, and increasing health care utilization for Veterans. In those whose TBI-related symptoms persist, there is accumulating evidence for increased morbidity (e.g., worse PTSD symptoms, chronic hypopituitarism, dementia), spurring efforts to improve diagnosis and intervention. Following a primary TBI injury, secondary injury and persistent symptoms may evolve through a complex cascade of events that culminate in inflammation, alterations in mitochondrial bioenergetics, and diminished blood brain barrier integrity, ultimately yielding a chronic disease state. To date, Veterans receiving strategy-based cognitive rehabilitation for TBI (CCT/CogSMART) have shown improvement in cognition and subjective neuropsychiatric symptoms. CCT is an evidence-based cognitive rehabilitation intervention emphasizing training in cognitive strategies to improve post-concussive symptoms, attention, learning/memory, and executive functioning. However, no pharmaceuticals have been developed for direct or adjunct-to CCT use to maximize treatment outcomes.

Given that inflammation has been observed in TBI, PTSD, and in co-occurring TBI/PTSD, it may be an important aspect of the TBI/PTSD disease state that could be manipulated to promote healing. The investigators are proposing to study TTI-0102, a cysteamine precursor that shows anti-inflammatory activity, as a potential adjunct to CCT for Veterans with TBI-related symptoms. TTI-0102 is a safe, easily administered, highly-water soluble compound that readily crosses the blood brain barrier. Compared with cysteamine, TTI-0102 degrades more slowly, dampening peak drug concentrations and sustaining drug plasma concentrations in a narrow therapeutic range. Developed to treat cystinosis, cysteamine is now believed to have potential for treatment of neurodegenerative disorders.

The goal of this proof of concept study is first, in Phase I (Year 1), to use symptom change (i.e., objective cognitive performance and subjective cognitive and neuropsychiatric symptoms) and biological profiles (i.e., metabolomics, inflammatory peptides \[interleukin-6 and C-reactive protein\], and brain-derived neurotrophic factor) to learn optimal dosing of TTI-0102 and to assess mechanism of action, and in Phase II (Year 2), to implement a feasibility trial in Veterans with a history of mild to moderate TBI and PTSD. In Phase I, 3 groups of 10 Veterans each will be randomly assigned to receive TTI-0102 2 grams/day, 4 grams/day, or placebo for 12 weeks. Baseline and post-treatment measures of objective cognition and subjective cognitive and neuropsychiatric symptoms will be administered, and plasma will be collected to measure the metabolomic, inflammatory, and protein biomarkers. In Phase II (Year 2), 12 different Veterans (6 per group) will be enrolled in a pilot randomized controlled trial (RCT) to assess the feasibility and acceptability of trial procedures. Participants in Phase II will be randomized to receive TTI-0102 (dose determined in Phase I) or placebo for 12 weeks as an adjunct to evidence-based CCT. The results of these double-blind, placebo-controlled trials will be used to plan a larger, fully-powered trial.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Mild to Moderate TBI Posttraumatic Stress Disorder

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Doses of drug and placebo will be prepared in identical sachets, with group assignment known only to the research pharmacist.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

TTI-0102 2 mg/day

TTI-0102 2 mg/day

Group Type EXPERIMENTAL

TTI-0102

Intervention Type DRUG

TTI-0102 is a cysteamine precursor.

TTI-0102 4 mg/day

TTI-0102 4 mg/day

Group Type EXPERIMENTAL

TTI-0102

Intervention Type DRUG

TTI-0102 is a cysteamine precursor.

Placebo

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

TTI-0102

TTI-0102 is a cysteamine precursor.

Intervention Type DRUG

Placebo

Placebo

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Elizabeth W. Twamley, PhD

Role: PRINCIPAL_INVESTIGATOR

VA San Diego Healthcare System, San Diego, CA

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

VA San Diego Healthcare System, San Diego, CA

San Diego, California, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

I21RX003323-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N3323-P

Identifier Type: -

Identifier Source: org_study_id