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

Sponsor

Michael E. DeBakey VA Medical Center (U.S. Fed)

Overall Status

Withdrawn

CT.gov ID

NCT00641511

Collaborator

Tuscaloosa Veterans Affairs Medical Center (U.S. Fed), Ralph H. Johnson VA Medical Center (U.S. Fed), Acorda Therapeutics (Industry)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Post Traumatic Stress Disorder (PTSD)	Drug: SYN117 (nepicastat) Drug: Placebo comparator	Phase 2

Detailed Description

The primary treatment objective is to assess the global efficacy of nepicastat in the treatment of hyper-arousal in Post Traumatic Stress Disorder (PTSD) in conflict or combat zone experienced veterans, in comparison to placebo. The secondary treatment objectives are to assess the ability of nepicastat to induce PTSD remission; treat PTSD and other PTSD symptom clusters and improve quality of life and overall functioning. A medical safety objective is to assess the tolerability and side effects of nepicastat in the treatment of PTSD in veterans who served in conflict zones at least one time between 1990 -2008 [includes Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF), Afghanistan, Gulf War, etc .

This is a 6-week study with the long-term objective is to define the best approach to treating PTSD and enhancing the quality of life in patients. Results from this pilot study will assist clinicians in treating active military service members or veterans with PTSD by developing new treatment algorithms for future larger studies.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Pharmacogenetic Clinical Trial of Nepicastat for PTSD

Study Start Date :

Jun 1, 2008

Actual Primary Completion Date :

Sep 1, 2009

Actual Study Completion Date :

Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 (Medication arm - SYN117 aka Nepicastat) 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) 120 mg per day Other Names: nepicastat
Placebo Comparator: 2 (Placebo arm) 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 once per day placebo capsules

Arm

Intervention/Treatment

Experimental: 1 (Medication arm - SYN117 aka Nepicastat)

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)

120 mg per day

Other Names:

nepicastat

Placebo Comparator: 2 (Placebo arm)

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

once per day placebo capsules

Outcome Measures

Primary Outcome Measures

Change from baseline in CAPS(D) hyperarousal scores as compared to placebo [6 weeks]

Secondary Outcome Measures

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]
Change from baseline in Sheehan Disability Scale as compared to placebo [6 weeks]
Change from baseline in Clinician Administered PTSD Scale- Symptom (CAPS-SX) as compared to placebo [6 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
18 to 65 years of age

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tuscaloosa VAMC	Tuscaloosa	Alabama	United States	35404
2	Ralph H. Johnson VA Medical Center	Charleston	South Carolina	United States	29401
3	Michael E. Debakey VAMC	Houston	Texas	United States	77030

Sponsors and Collaborators

Michael E. DeBakey VA Medical Center
Tuscaloosa Veterans Affairs Medical Center
Ralph H. Johnson VA Medical Center
Acorda Therapeutics

Investigators

Study Chair: Thomas Kosten, MD, Baylor College of Medicine, and DeBakey VAMC
Study Director: Lori Davis, MD, Tuscaloosa VAMC
Principal Investigator: Mark Hamner, MD, Ralph H Johnson VAMC
Principal Investigator: David P. Graham, MD, Michael E. DeBakey VA Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Thomas Kosten, MD, , Waggoner Chair and Professor of Psychiatry, Neuroscience, Pharmacology, Immunology & Pathology, Michael E. DeBakey VA Medical Center

ClinicalTrials.gov Identifier:

NCT00641511

Other Study ID Numbers:

H22601
Inv117-Kosten-CL01

First Posted:

Mar 24, 2008

Last Update Posted:

Aug 21, 2019

Last Verified:

Aug 1, 2019

Keywords provided by Thomas Kosten, MD, , Waggoner Chair and Professor of Psychiatry, Neuroscience, Pharmacology, Immunology & Pathology, Michael E. DeBakey VA Medical Center

PTSD

Additional relevant MeSH terms:

Stress Disorders, Traumatic

Stress Disorders, Post-Traumatic

Study Results

No Results Posted as of Aug 21, 2019