Effects of Paliperidone in Posttraumatic Stress Disorder (PTSD)

Posttraumatic Stress Disorder Clinical Trial

Official title:

Effects of Paliperidone in Posttraumatic Stress Disorder (PTSD)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00766064
• Other study ID #: 0804003717
• Status: Withdrawn
• Phase: Phase 4
• First received: September 30, 2008
• Last updated: August 22, 2016
• Start date: September 2008
• Est. completion date: November 2009

Study information

• Verified date: August 2016
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Chronic posttraumatic stress disorder (PTSD) is a debilitating disorder and treatment response to pharmacological interventions has been modest for these patients. Chronic elevated anxiety and associated psychophysiological parameters including increased heart rate and alterations in skin conductance are key symptoms of chronic PTSD. Antidepressants, including selective serotonin reuptake inhibitors (SRIs) or norepinephrine-serotonin re-uptake inhibitors are considered treatment of first choice for these patients, however a substantial portion of patients do not respond sufficiently (Zhang and Davidson 2007). Therefore, there is a need to establish novel and effective add-on treatment strategies for these patients. Recently, atypical neuroleptics have received considerable attention since it was shown in multiple controlled and naturalistic trials that these medications are an effective treatment option for patients with PTSD (Davis et al 2006). In chronic PTSD, the psychophysiological responses at baseline and in response to treatment have yet been inadequately studied and may provide novel insight into antidepressant and anxiolytic mechanisms of medications used in the treatment of PTSD. Therefore, in addition to evaluating the antidepressant and anxiolytic effects of paliperidone, a novel atypical neuroleptic, in the treatment of PTSD, we also aim to compare neurophysiological responses at baseline with post-treatment effects in antidepressant-refractory PTSD patients.

Primary Aim 1: Evaluate the anxiolytic and antidepressant effects of paliperidone in patients with PTSD.

Secondary Aim 2: Evaluate the effects of paliperidone on fear conditioned psychophysiological responses (including startle eyeblink, skin conductance, and cardiovascular inter-beat interval) at baseline and after 6 weeks of naturalistic treatment in chronic PTSD patients.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• willingness to participate in a naturalistic treatment study using paliperidone and in two fear conditioning tests, one at baseline and one at the end of the 6 weeks treatment study.

• We will include PTSD subjects on medications (possible medications include antidepressants, benzodiazepines) who have no or only partial treatment response. Paliperidone will be added to the existing treatment regime which will remain unchanged during the study period. PTSD subjects will have a minimum score of 50 on the Clinician-Administered PTSD Scale (CAPS; Blake et al, 1995).

Exclusion Criteria:

• a comorbid diagnosis of bipolar illness, schizophrenia or other psychotic disorders, acute or chronic suicidality, acute or chronic unstable medical conditions (including severely impaired hepatic function as indicated with abnormal PT and PTT, abnormal CBC, and liver enzymes more than 50% above the upper normal range, not well controlled blood pressure)

• current diagnosis of substance abuse or dependence

• unsuccessful treatment history with paliperidone

• known hypersensitivity to paliperidone or any of its inactive ingredients

• administration of any investigational drug up to 90 days before entry into the study

• intake of Class 1A (e.g., quinidine, procainamid) or Class III (e.g., amiodaronme, sotalol) antiarrhythmic medications, antipsychotics, antibiotics (e.g., gatifloxacin, moxifloxacin) (up to 90 days before entry into the study or during the study)

• subjects with a positive screen for drugs of abuse

• no startle or skin conductance response, or excessively high startle response to the startle probe (100 dB acoustic stimuli) during the pretest.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Disease
• Posttraumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Drug:
• Paliperidone
Paliperidone will be gradually increased to a final dose between 3 - 6 mg/day according to the following schedule: Weeks 1 - 3: 3 mg daily, Weeks 4 - 5: flexible dosing according clinical situation, dose range between 3 mg - 6 mg daily*, Week 6: fixed dose, *Criteria to increase the dose from 3 mg to 6 mg daily are 1] absence of any side effects, 2] patients not showing a sufficient response to 3 mg paliperidone can be increased to 6 mg daily. Response is defined as change in depression and anxiety ratings of at least 30% compared to baseline.

Locations

Country	Name	City	State
United States	VA Connecticut Healthcare System	West Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Behavioral ratings (e.g. MADRS, HAMA, CGI) and psychophysiological measures. Neurophysiological measurements of startle eyeblink, skin conductance, and cardiovascular inter-beat interval will be done.		behavioral ratings: weekly; Neurophysiological measurements will be done at baseline, before initiation of treatment with paliperidone (baseline) and after 6 weeks of paliperidone treatment.	No