Iloperidone for Symptoms of Arousal in Post Traumatic Stress Disorder (PTSD)

• ClinicalTrials.gov Identifier: NCT01917318
• Recruitment Status: Terminated
• First Posted: August 6, 2013
• Results First Posted: January 31, 2020
• Last Update Posted: February 11, 2020
• Sponsor: University of Colorado, Denver
• Collaborator: Novartis Pharmaceuticals
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

Brief Summary:

A Double-Blind Placebo-Controlled Random Order Crossover Pilot Study of Iloperidone for Symptoms of Arousal in PTSD.

Condition or disease	Intervention/treatment	Phase
Post Traumatic Stress Disorder	Drug: Iloperidone; Drug: Placebo	Phase 2

Detailed Description:

During Period A, subjects will receive 8 weeks of iloperidone or placebo (2 weeks titration period followed by 6 weeks on stable dose). Then they will be reassessed for response during Period A; study drug will be discontinued and washed out over the following 2 weeks. They will then begin Period B on the alternate blinded treatment with similar titration and assessment, initially weekly and then every other week for a total of another 8 weeks. The purpose of the study is to determine whether Iloperidone is effective in the treatment of some symptoms in patients with PTSD, particularly difficulty falling or staying asleep, trauma dreams and daytime irritability or outbursts.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Placebo-Controlled Random Order Crossover Study of Iloperidone for Symptoms of Arousal in PTSD Including Insomnia and Irritability.
• Study Start Date: July 2013
• Actual Primary Completion Date: February 2014
• Actual Study Completion Date: February 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Iloperidone / Placebo; During 1st treatment period subjects will receive iloperidone. During 2nd treatment period subjects will receive placebo.	Drug: Iloperidone; Subjects will receive oral iloperidone for 8 weeks. The first 2 weeks of treatment is called titration period and during this time the dose of iloperidone will be increased periodically from 1mg to a maximum of 8mg depending on response and tolerability. During the remaining 6 weeks of treatment, called stable dose period, the subjects will receive a stable dose of iloperidone(defined during titration period); Other Names: Fanapt; Fanapta; Zomaril; Drug: Placebo; During 8 weeks subjects will receive oral placebo; Other Name: Sugar pill
Experimental: Placebo / Iloperidone; During 1st treatment period subjects will receive placebo. During 2nd treatment period subjects will receive Iloperidone.	Drug: Iloperidone; Subjects will receive oral iloperidone for 8 weeks. The first 2 weeks of treatment is called titration period and during this time the dose of iloperidone will be increased periodically from 1mg to a maximum of 8mg depending on response and tolerability. During the remaining 6 weeks of treatment, called stable dose period, the subjects will receive a stable dose of iloperidone(defined during titration period); Other Names: Fanapt; Fanapta; Zomaril; Drug: Placebo; During 8 weeks subjects will receive oral placebo; Other Name: Sugar pill

Outcome Measures

Primary Outcome Measures :

1. Change in Clinician Administered PTSD Scale (CAPS) Part B and D [ Time Frame: Randomization and at the end of each treatment period. Placebo treatment lasted 8 weeks. Iloperidone treatment lasted 2 weeks. ]

   The Clinician-Administered PTSD Scale (CAPS) is a structured interview used to diagnose and assess PTSD. Part B of CAPS evaluates symptoms of re-experiencing. Part D evaluates avoidance and numbing.

   CAPS-B scores range from 0 to 40 where higher scores indicate more symptoms. A score 0 means no re-experiencing symptoms.

   CAPS-D scores range form 0 to 56 and higher scores indicate more symptoms. A score 0 means no avoidance or numbing symptoms.

   The primary endpoint was changes in CAPS part B and D after 8 weeks of treatment.

Secondary Outcome Measures :

1. Number of Awakenings [ Time Frame: Randomization and after 1, 2, 4, 6 and 8 weeks of placebo treatment. Only 1 week of wrist actigraphy was recorded during iloperidone treatment . ]
   Number of awakenings was measured by wrist actigraphy and sleep logs. Actigraphy results were downloaded at each study visit. The mean value during placebo treatment was calculated. There was only 1 value during iloperidone treatment.
2. Aggression [ Time Frame: Randomization and 8 weeks of treatment, during both treatment periods ]
   Aggression was measured by the Modified Overt Aggression Scale (MOAS).This assessment measures four types of aggressive behavior (verbal, aggression against property, autoaggression, and physical aggression) . Total scores on the MOAS range from 0-40, with a higher score indicating more aggressive behavior.
3. Sleep Latency [ Time Frame: Randomization and after 1, 2, 4, 6 and 8 weeks of placebo treatment. Only 1 week of wrist actigraphy was recorded during iloperidone treatment . ]
   Sleep latency was measured by wrist actigraphy and sleep logs. Actigraphy results were downloaded at each study visit. The mean value during placebo treatment was calculated.There was only 1 value during iloperidone treatment
4. Wake-time After Sleep Onset (WASO) [ Time Frame: Randomization and after 1, 2, 4, 6 and 8 weeks of placebo treatment. Only 1 week of wrist actigraphy was recorded during iloperidone treatment . ]
   WASO was measured by wrist actigraphy and sleep logs. Actigraphy results were downloaded at each study visit. The mean value during placebo treatment was calculated.There was only 1 value during iloperidone treatment.
5. Suicidal Ideation [ Time Frame: Total course of the study. CSSRS was administered during each study visit. Suicidal ideation during lifetime and during the month prior to screening were also explored ]
   The presence of suicidal ideation was monitored over the course of the trial by the first section of the Columbia Suicide Severity Rating Scale (CSSRS). This first section of the scale consists of 5 questions that can be answered yes or no. The number of participants who reported experiencing suicidal ideation is reported.
6. Intensity of Suicidal Ideation [ Time Frame: Baseline ]

   Intensity of Suicidal Ideation was monitored over the course of the trial by the second section of the Columbia Suicide Severity Rating Scale (CSSRS). This section is only administered if the patient answers yes to the first section. The section consists of 5 questions that refer to the most severe level of ideation endorsed in the first section of the CSSRS. The total score ranges from 2 to 25, with a higher number indicating more intense ideation and greater risk.

   Only lifetime intensity of suicidal ideation was explored as the patient had no suicidal ideation from the month prior to beginning the study to the completion of the study

7. Suicidal Behavior [ Time Frame: Total course of the study. CSSRS was administered during each study visit. Suicidal ideation during lifetime and during the month prior to screening were also explored ]
   The presence and severity os suicidal behavior was monitored over the course of the trial by the third section of the Columbia Suicide Severity Rating Scale (CSSRS). This sections consists of questions about 5 suicidal behaviors and non-suicidal self injurious behavior and it can be answered yes or no. The number of participants who experienced suicidal behavior is reported.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 89 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• PTSD diagnosis

Exclusion Criteria:

• Pregnancy
• Traumatic Brain Injury greater than mild
• Primary sleep disorder
• Caffeinism
• Active substance use disorder
• Active suicidal risk
• Antipsychotic medication, antibiotics, sedatives, some antihypertensive or antiarrhythmic medication

Contacts and Locations

Locations

United States, Colorado

University of Colorado Depression Center; Clinical and Translational Research Center (CTRC)

Aurora, Colorado, United States, 80045

Sponsors and Collaborators

University of Colorado, Denver

Novartis Pharmaceuticals

Investigators

• Principal Investigator: Michael H Allen, M.D.; University of Colorado School of Medicine - Depression Center

More Information

Additional Information:

Depression Center - University of Colorado Denver 

Publications:

Citrome L. Iloperidone for schizophrenia: a review of the efficacy and safety profile for this newly commercialised second-generation antipsychotic. Int J Clin Pract. 2009 Aug;63(8):1237-48. doi: 10.1111/j.1742-1241.2009.02142.x.

David D, De Faria L, Mellman TA. Adjunctive risperidone treatment and sleep symptoms in combat veterans with chronic PTSD. Depress Anxiety. 2006;23(8):489-91. doi: 10.1002/da.20187.

Krystal JH, Rosenheck RA, Cramer JA, Vessicchio JC, Jones KM, Vertrees JE, Horney RA, Huang GD, Stock C; Veterans Affairs Cooperative Study No. 504 Group. Adjunctive risperidone treatment for antidepressant-resistant symptoms of chronic military service-related PTSD: a randomized trial. JAMA. 2011 Aug 3;306(5):493-502. doi: 10.1001/jama.2011.1080.

Kobayashi I, Boarts JM, Delahanty DL. Polysomnographically measured sleep abnormalities in PTSD: a meta-analytic review. Psychophysiology. 2007 Jul;44(4):660-9. doi: 10.1111/j.1469-8986.2007.537.x. Epub 2007 May 22.

Monnelly EP, Ciraulo DA, Knapp C, Keane T. Low-dose risperidone as adjunctive therapy for irritable aggression in posttraumatic stress disorder. J Clin Psychopharmacol. 2003 Apr;23(2):193-6. doi: 10.1097/00004714-200304000-00012.

Raskind MA, Peskind ER, Hoff DJ, Hart KL, Holmes HA, Warren D, Shofer J, O'Connell J, Taylor F, Gross C, Rohde K, McFall ME. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry. 2007 Apr 15;61(8):928-34. doi: 10.1016/j.biopsych.2006.06.032. Epub 2006 Oct 25.

Reich DB, Winternitz S, Hennen J, Watts T, Stanculescu C. A preliminary study of risperidone in the treatment of posttraumatic stress disorder related to childhood abuse in women. J Clin Psychiatry. 2004 Dec;65(12):1601-6. doi: 10.4088/jcp.v65n1204.

Taylor FB, Martin P, Thompson C, Williams J, Mellman TA, Gross C, Peskind ER, Raskind MA. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008 Mar 15;63(6):629-32. doi: 10.1016/j.biopsych.2007.07.001. Epub 2007 Sep 14.

Wicklow A, Espie CA. Intrusive thoughts and their relationship to actigraphic measurement of sleep: towards a cognitive model of insomnia. Behav Res Ther. 2000 Jul;38(7):679-93. doi: 10.1016/s0005-7967(99)00136-9.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01917318
• Other Study ID Numbers: 13-0207; IIRP-1371 ( Other Identifier: Novartis pharmaceuticals )
• First Posted: August 6, 2013
• Results First Posted: January 31, 2020
• Last Update Posted: February 11, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University of Colorado, Denver:

Post traumatic stress disorder; Treatment of post traumatic stress disorder; Symptoms of arousal in post traumatic stress disorder; Iloperidone in post traumatic stress disorder

Additional relevant MeSH terms:

Disease; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Pathologic Processes; Trauma and Stressor Related Disorders; Mental Disorders; Iloperidone; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Psychotropic Drugs