Pharmacogenetic Clinical Trial of Nepicastat for Post Traumatic Stress Disorder (PTSD)

NCT00641511 | Withdrawn Phase 2 DMC

• 2 other identifiers: H22601Inv117-Kosten-CL01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

Assess the effect of nepicastat in the treatment of in Post Traumatic Stress Disorder (PTSD) in conflict or combat zone experienced veterans, in comparison to placebo.

Conditions

Post Traumatic Stress Disorder (PTSD)

Keywords

PTSD

Outcome Measures

Primary Outcomes (1)

• Change from baseline in CAPS(D) hyperarousal scores as compared to placebo

  6 weeks

Secondary Outcomes (7)

• Change from baseline in Structured Interview of Posttraumatic Stress Disorder (SIP) as compared to placebo

  6 weeeks

• Change from baseline in Montgomery Asberg Depression Rating Scale (MADRS)as compared to placebo

  6 weeks

• Clinicians global impression of Severity and Improvement

  6 weeks

• Quality of life assessment as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).

  6 weeks

• Change from baseline in Davidson Trauma Scale (DTS) as compared to placebo

  6 weeks

Study Arms (2)

1 (Medication arm - SYN117 aka Nepicastat)

EXPERIMENTAL

Veterans will be receiving the study medication Nepicastat initiated with a 3-day loading phase of 40 mg on day 1, 80 mg on day 2 and 120 mg on day 3 (orally) and be continued at 120 mg once daily; During the 8 weeks (weeks: 7-14) extension phase, those from both treatment groups of the RCT phase will start open-label, active Nepicastat (i.e. no chance of placebo) treatment and be followed for an additional 8 weeks. Those who have a prior defined positive clinical response to the study medication, Nepicastat, will be continued on open label Nepicastat at 120mg once daily, in order to assess further improvement and safety; those who do not have a positive clinical response during the 6 weeks RCT will be offered the addition of the standard first-line PTSD pharmacotherapy, Paroxetine. Paroxetine is an allowed concomitant medication (i.e. "rescue medication") and is not considered a research medication or subject of a research question during the 8 weeks extension phase.

Drug: SYN117 (nepicastat)

2 (Placebo arm)

PLACEBO COMPARATOR

During the 6 weeks ( weeks: 1-6) double- blind, randomized clinical trial (RCT) phase, the veterans who have been randomized to the placebo treatment group will be receiving placebo pills. During the 8 weeks (weeks: 7-14) extension phase, all veterans from both treatment groups of the RCT phase will start open-label, active Nepicastat (i.e. no chance of placebo) treatment and be followed by the study team for an additional 8 weeks. The veterans on the placebo during the RCT will receive the study medication at end of the study week 6, the medication will be initiated with a 3-day loading phase of 40 mg on day 1, 80 mg on day 2 and 120 mg on day 3 (orally) and be continued at 120 mg once daily for 8 weeks until the end of the study.

Drug: Placebo comparator

Interventions

SYN117 (nepicastat) DRUG

120 mg per day

Also known as: nepicastat

1 (Medication arm - SYN117 aka Nepicastat)

Placebo comparator DRUG

once per day placebo capsules

2 (Placebo arm)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Patient understands the risks and benefits and agrees to visit frequency and procedures
• Male or female
• Any race or ethnic origin
• Served in conflict zones at least one time between 1990 -2008 \[includes Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF), Afghanistan, Gulf War, etc\]
• Currently Active Duty, National Guard, Reservist, Veteran, and/or Retired Military
• DSM-IV Diagnosis of Post-Traumatic Stress Disorder (PTSD)
• No substance use disorders (except for nicotine and caffeine) in the previous 2 months
• Free of psychotropic medication for 2 weeks prior to randomization (a low dose sedative hypnotic is allowed for severe insomnia if used sparingly)
• Physical and laboratory panel are within normal limits or not clinically significant
• Women of childbearing potential must be using medically-approved methods of birth control
• to 65 years of age

You may not qualify if:

• Lifetime history of bipolar I, schizophrenia, schizoaffective or cognitive disorders
• Actively considering plans of suicide or homicide
• Psychotic symptoms that in the investigator's opinion impair the patient's ability to give informed consent or make it unsafe for patient to be maintained without a neuroleptic
• Unstable general medical conditions or a contraindication to the use of nepicastat
• Intolerable side effects or allergic reaction to nepicastat
• Women planning to become pregnant or breastfeed during the study

Sponsors & Collaborators

• Michael E. DeBakey VA Medical Center: lead
• Tuscaloosa Veterans Affairs Medical Center: collaborator
• Ralph H. Johnson VA Medical Center: collaborator
• Acorda Therapeutics: collaborator

Study Sites (3)

Tuscaloosa VAMC

Tuscaloosa, Alabama, 35404, United States

Location

Ralph H. Johnson VA Medical Center

Charleston, South Carolina, 29401, United States

Location

Michael E. Debakey VAMC

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

nepicastat

Condition Hierarchy (Ancestors)

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

Study Officials

• Thomas Kosten, MD

  Baylor College of Medicine, and DeBakey VAMC

  STUDY CHAIR

• Lori Davis, MD

  Tuscaloosa VAMC

  STUDY DIRECTOR

• Mark Hamner, MD

  Ralph H Johnson VAMC

  PRINCIPAL INVESTIGATOR

• David P. Graham, MD

  Michael E. DeBakey VA Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: , Waggoner Chair and Professor of Psychiatry, Neuroscience, Pharmacology, Immunology & Pathology

Study Record Dates

• First Submitted: March 18, 2008
• First Posted: March 24, 2008
• Study Start: June 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: November 1, 2009
• Last Updated: August 21, 2019

Record last verified: 2019-08

Locations

US (3)