Substance P Antagonist in the Treatment of Posttraumatic Stress Disorder
Condition: PTSD
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): 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 type(s): Drug; Procedure; Procedure; Procedure; Procedure; Procedure; Procedure; Procedure; Procedure
Intervention MeSH terms: Vofopitant
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: PTSD; Substance P; Treatment Study; Placebo; Controlled; Post Traumatic Stress Disorder