Ignite Creation Date:
2024-05-05 @ 4:54 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00330291
Status:
WITHDRAWN
Last Update Posted:
2012-09-07
First Post:
2006-05-24
Brief Title:
Xyrem for Treatment Refractory Insomnia Due to PTSD
Sponsor:
State University of New York - Upstate Medical University
Organization:
State University of New York - Upstate Medical University
Study Overview
Official Title:
Xyrem for Treatment Refractory Insomnia Due to PTSD
Status:
WITHDRAWN
Status Verified Date:
2012-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
terminated due to inability to recruit subjects
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Xyrem sodium oxybate is an agent with the propensity to improve slow wave sleep and sleep efficiency It is FDA approved to treat cataplexy drop attacks associated with narcolepsy sleep attacks It has been shown to be a safe and effective agent here where deep restorative slow wave sleep improves and next day cataplexy attacks tend not to occur
Post Traumatic Stress Disorder PTSD is a psychiatric illness where a patient has witnessed or been involved in a traumatic event After the event is over nightmares flashbacks avoidance of people and places associated with trauma and hyperarousal occur which is incapacitating to the patient One major part of PTSD hyperarousal is marked insomnia with multiple awakenings at night This resultant poor sleep is compounded by use of SSRI serotonergic antianxiety agents ie Zoloftsertraline as first line therapy which tend to degrade slow wave restorative sleep Patients may respond to SSRI treatment but may fail to remit as they continue to have sleep problems PTSD patients will often fail to respond to antihistamine Desyrel trazodone and benzodiazepine GABA hypnotic agents Restoriltemazepam and continue with poor interrupted sleep It is possible that Xyrems ability to remarkably improve slow wave sleep may greatly help treatment refractory insomnia due to PTSD
The author proposes an open-label study no placebo where 10 PTSD patients who have failed usual PTSD treatments and have failed usual insomnia treatments in particular will be given Xyrem in addition to their current PTSD medication The authors wish to determine if Xyrem is a safe treatment optionin this difficult-to-treat patient population
Post Traumatic Stress Disorder PTSD is a psychiatric illness where a patient has witnessed or been involved in a traumatic event After the event is over nightmares flashbacks avoidance of people and places associated with trauma and hyperarousal occur which is incapacitating to the patient One major part of PTSD hyperarousal is marked insomnia with multiple awakenings at night This resultant poor sleep is compounded by use of SSRI serotonergic antianxiety agents ie Zoloftsertraline as first line therapy which tend to degrade slow wave restorative sleep Patients may respond to SSRI treatment but may fail to remit as they continue to have sleep problems PTSD patients will often fail to respond to antihistamine Desyrel trazodone and benzodiazepine GABA hypnotic agents Restoriltemazepam and continue with poor interrupted sleep It is possible that Xyrems ability to remarkably improve slow wave sleep may greatly help treatment refractory insomnia due to PTSD
The author proposes an open-label study no placebo where 10 PTSD patients who have failed usual PTSD treatments and have failed usual insomnia treatments in particular will be given Xyrem in addition to their current PTSD medication The authors wish to determine if Xyrem is a safe treatment optionin this difficult-to-treat patient population
Detailed Description:
This is an open-label no placebo study to see if the addition of Xyrem to a subjects PTSD medication regimen will be tolerated and possibly improve insomnia Subjects will currently be taking at least a single psychotropic agent for the treatment of PTSD an SSRI Dosing will be stable for at least 4 weeks and subjects will need to report continued insomnia despite treatment They must also have failed at least two insomnia augmentations from separate drugs classes benzodiazepine temezapam zolpidem ect antihistime quetiapine mirtazapine trazadone etc dopamine antagonist olanzapine quetiapine aripiprazole etc to qualify for refractory insomnia
Subjects will complete consenting process and attend a screening visit where they will be given a MINI psychiatric diagnostic evaluation to confirm PTSD be given a Hamilton Anxiety a Hospital Anxiety Depression Scale PCL-C Fatigue Severity Scale Epworth Sleepiness Scale Pittsburgh Sleep Quality Inventory SF-12 and sleep diary evaluation to delineate current anxiety levels secondary measure Subjects will have to offer consent for the study team to contact their primary providers and retrieve all past and present records to show refractory history and lack of substance abuse Subjects will undergo a brief physical exam and bloodwork and a sleep EEG will be ordered Furthermore a urine drug screen will be used to screen for current misuse If subjects are taking sleeping agents they will be appropriately washed out tapered per cusual clinical practice and then drug free 5 times the drugs half life prior to sleep EEG and prior to Xyrem start In clinical practice Xyrem use does not warrant blood monitoring EEGs or EKGs per the FDA
Assuming subject meets eligibility they will start Xyrem per cataplexy dosing guidelines Prior to titration a 1-2 week washout of any sleeping agent will occur Titration will then start with 225g at bedtime and then again 4 hours later This drug may be flexibly increased to 45g x2 doses based upon tolerability and effectiveness We will escalate dose if drug is toleratedbut without efficacy Dosing will be increased if subjective sleep quantityquality is still reported to be unchanged or if our rating scales indicate minimal to no change
After screening visit 1 eligibility medical safety determination washout sleep EEG subjects will return for baseline Visit 2 and start Xyrem
They will be seen for Visit 3 after 7 days of treatment for rating scales and possible dose escalation to 6gd
They will be seen for Visit 4 after 14 days of treatment for rating scales and possible dose escalation to 75gd
They will be seen for Visit 5 after 21 days of treatment for rating scales and possible dose escalation to 9gd
They will be seen for Visit 6termination after 28 days of treatment for rating scales physical exam lab work sleep EEG
Subjects will be called for final safety follow up one week later and 12 weeks later
Again liaison with the subjects provider will occur to discuss continuance of Xyrem If provider agrees then long term monitoring will be in the jurisdiction of this provider If agreement is to NOT continue Xyrem patient will be tapered or offered help in finding a clinician comfortable with the drug There is no major issue in stopping this drug from a withdrawal point of view as it does not build up in the system over time in regards to dependence when used at bed time only Insomnia will likely return and patient would go back to their usual treatment if desired and most likely their original level of insomnia
Safety Measures The overall safety and tolerability of Xyrem will be assessed throughout the study by adverse event recording clinical laboratory test results and physical exams A Safety monitoring board will consist of the PI and two psychiatry attendings from University Hospital
Subjects will complete consenting process and attend a screening visit where they will be given a MINI psychiatric diagnostic evaluation to confirm PTSD be given a Hamilton Anxiety a Hospital Anxiety Depression Scale PCL-C Fatigue Severity Scale Epworth Sleepiness Scale Pittsburgh Sleep Quality Inventory SF-12 and sleep diary evaluation to delineate current anxiety levels secondary measure Subjects will have to offer consent for the study team to contact their primary providers and retrieve all past and present records to show refractory history and lack of substance abuse Subjects will undergo a brief physical exam and bloodwork and a sleep EEG will be ordered Furthermore a urine drug screen will be used to screen for current misuse If subjects are taking sleeping agents they will be appropriately washed out tapered per cusual clinical practice and then drug free 5 times the drugs half life prior to sleep EEG and prior to Xyrem start In clinical practice Xyrem use does not warrant blood monitoring EEGs or EKGs per the FDA
Assuming subject meets eligibility they will start Xyrem per cataplexy dosing guidelines Prior to titration a 1-2 week washout of any sleeping agent will occur Titration will then start with 225g at bedtime and then again 4 hours later This drug may be flexibly increased to 45g x2 doses based upon tolerability and effectiveness We will escalate dose if drug is toleratedbut without efficacy Dosing will be increased if subjective sleep quantityquality is still reported to be unchanged or if our rating scales indicate minimal to no change
After screening visit 1 eligibility medical safety determination washout sleep EEG subjects will return for baseline Visit 2 and start Xyrem
They will be seen for Visit 3 after 7 days of treatment for rating scales and possible dose escalation to 6gd
They will be seen for Visit 4 after 14 days of treatment for rating scales and possible dose escalation to 75gd
They will be seen for Visit 5 after 21 days of treatment for rating scales and possible dose escalation to 9gd
They will be seen for Visit 6termination after 28 days of treatment for rating scales physical exam lab work sleep EEG
Subjects will be called for final safety follow up one week later and 12 weeks later
Again liaison with the subjects provider will occur to discuss continuance of Xyrem If provider agrees then long term monitoring will be in the jurisdiction of this provider If agreement is to NOT continue Xyrem patient will be tapered or offered help in finding a clinician comfortable with the drug There is no major issue in stopping this drug from a withdrawal point of view as it does not build up in the system over time in regards to dependence when used at bed time only Insomnia will likely return and patient would go back to their usual treatment if desired and most likely their original level of insomnia
Safety Measures The overall safety and tolerability of Xyrem will be assessed throughout the study by adverse event recording clinical laboratory test results and physical exams A Safety monitoring board will consist of the PI and two psychiatry attendings from University Hospital
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None