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Clinical Trials/NCT00383786
NCT00383786CompletedPhase 2

Evaluation of the Efficacy of the NK1 Antagonist GR205171 in Posttraumatic Stress Disorder

Baylor College of Medicine2 sites in 1 country47 target enrollmentStarted: September 2006Last updated:
Conditions
Interventions
Drugs

Trial Snapshot

Phase
Phase 2
Status
Completed
Enrollment
47
Locations
2
Primary Endpoint
Changes in CAPS Scores.

Study Overview

Brief Summary

This study, conducted at the NIH and the Mount Sinai School of Medicine, will examine the effectiveness of a substance P or NK1 antagonist study drug known as GR205171 in treating the symptoms of posttraumatic stress disorder (PTSD).

People between 18 and 65 years of age who have been diagnosed with PTSD may be eligible for this study. Participants undergo the following tests and procedures:

Treatment: Patients are tapered off current ineffective medications over 1 to 2 weeks. All participants receive placebo (sugar pill) at the start of the study. At some point within the first 3 weeks of the study, they are then randomly assigned either to take GR205171 or to continue with placebo for the remainder of the 10-week treatment period.

Clinic visits: Patients come to the clinic once a week during treatment. The following procedures are done at various visits.

  • Interviews, self report questionnaires and psychiatric rating scales at every visit.
  • Physical examination, blood and urine tests. Blood is drawn up to 10 times during the study.

Follow-up visits continue for up to 3 months after the end of the study, during which patients are offered standard clinical treatment.

Detailed Description

Posttraumatic Stress Disorder (PTSD) is a common chronic anxiety disorder that is often debilitating and follows exposure to an overwhelming traumatic event. The burden of PTSD on individuals and society is significant. The majority of PTSD sufferers also meet the diagnostic criteria for several other psychiatric disorders and many attempt suicide. Despite the devastating impact of PTSD on the lives of millions worldwide, little is known about the etiology or pathophysiology of this disorder. Although disruptions in the hypothalamic-pituitary adrenal (HPA) Axis, noradrenergic, serotonergic systems have been proposed as neurobiological substrates in the development of PTSD, the exact underpinnings of the neurobiology of PTSD remain to be fully elucidated.

PTSD is responsive to treatment with selective serotonin reuptake inhibitors, but response rates rarely exceed 60%, and even fewer patients (20%-30%) experience improvement that could be characterized as remission. Thus, there is a clear need to develop novel and improved therapeutics for PTSD. A growing body of preclinical evidence suggests that activation of the Substance P (SP) and its receptor NK1 is anxiogenic and that NK1 antagonists, upon chronic administration, exert significant dampening (albeit complex) effects on the SP-NP system. Furthermore, several stress paradigms are believed to exert many of their deleterious effects on hippocampal structures via enhancement of SP-NK1 system. Overall, excess activity of the SP-NK1 system stands as a prime candidate for involvement in the pathophysiology of anxiety disorders such as PTSD.

In this study, we propose to investigate the potential antianxiety efficacy of the highly specific NK1 antagonist GR205171 in PTSD. Furthermore, we propose to, in a preliminary fashion, longitudinally investigate whether neuroendocrine surrogate markers are predictive of treatment response.

This is an 8-week double-blind placebo-controlled study that will examine the efficacy and safety of an NK1 antagonist in patients with PTSD.

Patients, ages 18 to 65 years with a diagnosis of PTSD, will in this pilot study be randomized to double-blind treatment to receive either the NK1 antagonist, GR205171 (5 mg/day) or placebo for a period of 8 weeks.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)

Eligibility Criteria

Ages
18 Years to 65 Years (Adult, Older Adult)
Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Not provided

Exclusion Criteria

  • Not provided

Arms & Interventions

GR205171

Experimental

selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.

Intervention: NK1 Antagoist (GR205171) (Drug)

GR205171

Experimental

selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.

Intervention: Psychophysiology (Trauma Script) (Procedure)

GR205171

Experimental

selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.

Intervention: Psychophysiology (Verbal Threat) (Procedure)

GR205171

Experimental

selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.

Intervention: Psychophysiology (Fear Conditioning) (Procedure)

placebo

Placebo Comparator

sugar pill

Intervention: Psychophysiology (Fear Conditioning) (Procedure)

placebo

Placebo Comparator

sugar pill

Intervention: Psychophysiology (Affective Modulation) (Procedure)

GR205171

Experimental

selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.

Intervention: Psychophysiology (Affective Modulation) (Procedure)

GR205171

Experimental

selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.

Intervention: Psychophysiology (Heart rate variability) (Procedure)

GR205171

Experimental

selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.

Intervention: Lumbar Puncture (Procedure)

GR205171

Experimental

selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.

Intervention: 24-hour plasma sampling (Procedure)

GR205171

Experimental

selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.

Intervention: MRI (Procedure)

placebo

Placebo Comparator

sugar pill

Intervention: Psychophysiology (Trauma Script) (Procedure)

placebo

Placebo Comparator

sugar pill

Intervention: Psychophysiology (Verbal Threat) (Procedure)

placebo

Placebo Comparator

sugar pill

Intervention: Psychophysiology (Heart rate variability) (Procedure)

placebo

Placebo Comparator

sugar pill

Intervention: Lumbar Puncture (Procedure)

placebo

Placebo Comparator

sugar pill

Intervention: 24-hour plasma sampling (Procedure)

placebo

Placebo Comparator

sugar pill

Intervention: MRI (Procedure)

Outcomes

Primary Outcomes

Changes in CAPS Scores.

Time Frame: Baseline, 8 weeks

The Clinician-Administered PTSD Scale (CAPS) is the gold standard in PTSD assessment. The CAPS is a 30-item structured interview that corresponds to the DSM-IV criteria for PTSD. This is a 17-item core symptom scale, measuring both frequency and intensity of symptoms, with the most frequently used scoring rule is to count a symptom as present if it has a frequency of 1 or more and an intensity of 2 or more. A PTSD diagnosis is made if there is at least 1 "B" symptom, 3 "C" symptoms, and 2 "D" symptoms as well as meeting the other diagnostic criteria. Scores range from 0-136 0 (best possible outcome) to 136 (worst possible outcome). The relevant time-points for reporting change were at baseline and 8 weeks.

Secondary Outcomes

No secondary outcomes reported

Investigators

Sponsor Class
Other
Responsible Party
Principal Investigator
Principal Investigator

Sanjay Johan Mathew

MD

Baylor College of Medicine

Study Sites (2)

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