Substance P Antagonist in the Treatment of Posttraumatic Stress Disorder
Condition: PTSD
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: NK1 Antagoist (GR205171); Psychophysiology (Trauma Script); Psychophysiology (Verbal Threat); Psychophysiology (Fear Conditioning); Psychophysiology (Affective Modulation); Psychophysiology (Heart rate variability); Lumbar Puncture; 24-hour plasma sampling; MRI
Intervention MeSH terms: Vofopitant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: PTSD; Substance P; Treatment Study; Placebo; Controlled; Post Traumatic Stress Disorder

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Subjects may be included in the study only if they meet all of the following criteria:

          1. Male or female subjects, 18 to 65 years.

          2. Female subjects of childbearing potential must be using a medically accepted means of
             contraception.

          3. Each subject must have a level of understanding sufficient to agree to all required
             tests and examinations and sign an informed consent document.

          4. A negative urine toxicology.

          5. 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.

          6. Duration of illness of PTSD for at least 3 months.

          7. Subjects must have an initial score at Visit 1 and Visit 2 of at least 50 on the CAPS
             for PTSD Studies.

          8. Subjects must not have a decrease in the total score of CAPS of greater than 25%
             during washout (between Visits 1 and 2).

        EXCLUSION CRITERIA:

        Subjects will be excluded from the study for any of the following reasons:

          1. Presence of psychotic features.

          2. Participation in a clinical trial of another investigational drug within 1 month (30
             days) prior to study entry (Visit 1).

          3. Female subjects who are either pregnant or nursing.

          4. Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory,
             cardiovascular (including ischemic heart disease), endocrinologic, neurologic,
             immunologic, or hematologic disease.

          5. Subjects with uncorrected hypothyroidism or hyperthyroidism.

          6. Previous treatment with NK1 receptor antagonist.

          7. DSM-IV substance abuse or dependence within the past 90 days.

          8. Treatment with an injectable depot neuroleptic within less than one dosing interval
             between depot neuroleptic injections prior to Visit 2.

          9. Treatment with a reversible MAOI, guanethidine, or guanadrel within 1 week or with
             fluoxetine within 6 weeks prior to Visit 2.

         10. Treatment with any other concomitant medication with primarily CNS activity.

         11. Treatment with clozapine or ECT within 12 weeks prior to Visit 2.

         12. 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.

         13. Patients who are currently at high risk for homicide or suicide, a score greater than
             4 on item 10 of the MADRS.

         14. Current or planned litigation regarding the traumatic event.

        Patients will not be allowed to receive structured psychotherapy during the trial.