Substance P Antagonist in the Treatment of Posttraumatic Stress Disorder

Phase 2

Completed

• Conditions: PTSD
• Interventions: Drug: NK1 Antagoist (GR205171); Procedure: Psychophysiology (Trauma Script); Procedure: Psychophysiology (Verbal Threat); Procedure: Psychophysiology (Fear Conditioning); Procedure: Psychophysiology (Affective Modulation); Procedure: Psychophysiology (Heart rate variability); Procedure: 24-hour plasma sampling; Procedure: Lumbar Puncture; Procedure: MRI

• Registration Number: NCT00383786
• Lead Sponsor: Baylor College of Medicine

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.

Approximately 52 patients will enter the study to obtain 40 subjects who complete the 8 weeks of acute NK1 antagonist treatment.

Study Timeline

• Study Start: 2006-09
• Study First Submitted: 2006-10-03
• Study First Submitted QC: 2006-10-03
• Study First Posted: 2006-10-04
• Primary Completion: 2009-06
• Study Completion: 2009-06
• Results First Submitted: 2013-09-05
• Results First Submitted QC: 2013-12-27
• Results First Posted: 2014-01-31
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-16
• Last Update Posted: 2019-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GR205171	Psychophysiology (Heart rate variability)	selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.
GR205171	Psychophysiology (Verbal Threat)	selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.
GR205171	Psychophysiology (Affective Modulation)	selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.
GR205171	Psychophysiology (Trauma Script)	selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.
GR205171	Psychophysiology (Fear Conditioning)	selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.
GR205171	MRI	selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.
placebo	Psychophysiology (Trauma Script)	sugar pill
placebo	Psychophysiology (Verbal Threat)	sugar pill
placebo	24-hour plasma sampling	sugar pill
GR205171	NK1 Antagoist (GR205171)	selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.
GR205171	Lumbar Puncture	selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.
GR205171	24-hour plasma sampling	selective neurokinin-1 receptor antagonist, fixed 5 mg dose every day, for 8 weeks.
placebo	Lumbar Puncture	sugar pill
placebo	Psychophysiology (Fear Conditioning)	sugar pill
placebo	Psychophysiology (Affective Modulation)	sugar pill
placebo	Psychophysiology (Heart rate variability)	sugar pill
placebo	MRI	sugar pill

Primary Outcome Measures

Name	Time	Method
Changes in CAPS Scores.	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.

Trial Locations

Locations (2)

Mt. Sinai Medical Center; 🇺🇸 New York, New York, United States

National Institutes of Health Clinical Center, 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States