Substance P Antagonist in the Treatment of Posttraumatic Stress Disorder

NCT00383786 | Completed Phase 2 Results DMC

• 2 other identifiers: 06025306-M-0253
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

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.

Conditions

PTSD

Keywords

PTSD; Substance P; Treatment Study; Placebo; Controlled; Post Traumatic Stress Disorder

Outcome Measures

Primary Outcomes (1)

• Changes in CAPS Scores.

  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.

  Baseline, 8 weeks

Other Outcomes (1)

• Able to Identify Biological Markers That Predict Response to Treatment.

  10 weeks

Study Arms (2)

GR205171

EXPERIMENTAL

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

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: Lumbar Puncture; Procedure: 24-hour plasma sampling; Procedure: MRI

placebo

PLACEBO COMPARATOR

sugar pill

Procedure: Psychophysiology (Trauma Script); Procedure: Psychophysiology (Verbal Threat); Procedure: Psychophysiology (Fear Conditioning); Procedure: Psychophysiology (Affective Modulation); Procedure: Psychophysiology (Heart rate variability); Procedure: Lumbar Puncture; Procedure: 24-hour plasma sampling; Procedure: MRI

Interventions

NK1 Antagoist (GR205171) DRUG

GR205171

Psychophysiology (Trauma Script) PROCEDURE

GR205171; placebo

Psychophysiology (Verbal Threat) PROCEDURE

GR205171; placebo

Psychophysiology (Fear Conditioning) PROCEDURE

GR205171; placebo

Psychophysiology (Affective Modulation) PROCEDURE

GR205171; placebo

Psychophysiology (Heart rate variability) PROCEDURE

GR205171; placebo

Lumbar Puncture PROCEDURE

GR205171; placebo

24-hour plasma sampling PROCEDURE

GR205171; placebo

MRI PROCEDURE

GR205171; placebo

Eligibility Criteria

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

You may qualify if:

• Subjects may be included in the study only if they meet all of the following criteria:
• Male or female subjects, 18 to 65 years.
• Female subjects of childbearing potential must be using a medically accepted means of contraception.
• Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
• A negative urine toxicology.
• Subjects must fulfill the criteria for PTSD as defined in DSM-IV (309.81), which should be the primary diagnosis. Diagnoses are based on clinical assessment and confirmed by structured diagnostic interview SCID-P.
• Duration of illness of PTSD for at least 3 months.
• Subjects must have an initial score at Visit 1 and Visit 2 of at least 50 on the CAPS for PTSD Studies.
• Subjects must not have a decrease in the total score of CAPS of greater than 25% during washout (between Visits 1 and 2).

You may not qualify if:

• Subjects will be excluded from the study for any of the following reasons:
• Presence of psychotic features.
• Participation in a clinical trial of another investigational drug within 1 month (30 days) prior to study entry (Visit 1).
• Female subjects who are either pregnant or nursing.
• Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
• Subjects with uncorrected hypothyroidism or hyperthyroidism.
• Previous treatment with NK1 receptor antagonist.
• DSM-IV substance abuse or dependence within the past 90 days.
• Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to Visit 2.
• Treatment with a reversible MAOI, guanethidine, or guanadrel within 1 week or with fluoxetine within 6 weeks prior to Visit 2.
• Treatment with any other concomitant medication with primarily CNS activity.
• Treatment with clozapine or ECT within 12 weeks prior to Visit 2.
• Current diagnosis of schizophrenia or other psychotic disorder, bipolar disorder, other Axis I disorder (except for major depressive disorder, dysthymia and other anxiety disorders that followed exposure to the trauma) as defined in the DSM-IV.
• Patients who are currently at high risk for homicide or suicide, a score greater than 4 on item 10 of the MADRS.
• Current or planned litigation regarding the traumatic event.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029-0574, United States

Location

Related Publications (4)

• Agelink MW, Boz C, Ullrich H, Andrich J. Relationship between major depression and heart rate variability. Clinical consequences and implications for antidepressive treatment. Psychiatry Res. 2002 Dec 15;113(1-2):139-49. doi: 10.1016/s0165-1781(02)00225-1.

  PMID: 12467953 BACKGROUND

• Ballard TM, Sanger S, Higgins GA. Inhibition of shock-induced foot tapping behaviour in the gerbil by a tachykinin NK1 receptor antagonist. Eur J Pharmacol. 2001 Feb 2;412(3):255-64. doi: 10.1016/s0014-2999(01)00724-5.

  PMID: 11166289 BACKGROUND

• Bernstein EM, Putnam FW. Development, reliability, and validity of a dissociation scale. J Nerv Ment Dis. 1986 Dec;174(12):727-35. doi: 10.1097/00005053-198612000-00004.

  PMID: 3783140 BACKGROUND

• Mathew SJ, Vythilingam M, Murrough JW, Zarate CA Jr, Feder A, Luckenbaugh DA, Kinkead B, Parides MK, Trist DG, Bani MS, Bettica PU, Ratti EM, Charney DS. A selective neurokinin-1 receptor antagonist in chronic PTSD: a randomized, double-blind, placebo-controlled, proof-of-concept trial. Eur Neuropsychopharmacol. 2011 Mar;21(3):221-9. doi: 10.1016/j.euroneuro.2010.11.012. Epub 2010 Dec 30.

  PMID: 21194898 DERIVED

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

vofopitant; Psychophysiology; Spinal Puncture

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Behavioral Sciences; Behavioral Disciplines and Activities; Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

Limitations include the small sample size and brief duration of the trial, as 8 weeks might have been insufficient to test the efficacy of GR205171 for chronic PTSD. Sample size was also a limitation.

Results Point of Contact

• Title: Sanjay Mathew, MD/PI
• Organization: Baylor College of Medicine

sjmathew@bcm.edu

7137985439

Study Officials

• Dennis S Charney, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: October 3, 2006
• First Posted: October 4, 2006
• Study Start: September 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: July 31, 2019
• Results First Posted: January 31, 2014

Record last verified: 2019-07

Locations

US (2)