Xyrem and Brain Dopamine in Narcolepsy

Does Xyrem Influence Brain Dopamine in Patients With Narcolepsy? A PET Imaging Investigation

The overall aim of this investigation is to establish whether an action of Xyrem® on the brain dopamine system in patients with narcolepsy, and in a comparison control group, might explain part of the anti-narcoleptic effect of the drug.

Trial Objective is to establish, using positron emission tomography (PET), in Xyrem®-naïve narcolepsy with cataplexy patients, and in matched controls, whether a single dose of Xyrem® causes changes in striatal binding of 11C-raclopride and 11C-DTBZ that would suggest altered activity of brain dopamine neurones.

Study Overview

• Status: Completed
• Conditions: Healthy Controls; Narcolepsy With Cataplexy
• Intervention / Treatment: Drug: Xyrem

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 1R8
      • Centre for Addiction and Mental Health (CAMH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• current diagnosis of narcolepsy with cataplexy OR healthy control

Exclusion Criteria:

• use of any sedative hypnotics, tranquilizers, anticonvulsants, antihistamines (except non-sedating), benzodiazepines, clonidine or any medication known to affect dopamine at start of baseline period
• significant unstable or uncontrolled medical/psychiatric disease
• significant history of head trauma/surgery or seizure disorder
• radiation exposure exceeding 20mSv in last 12 months
• pregnancy
• substance abuse/dependence (including alcohol)
• have sleep apnea, or are shift workers
• on a sodium-restricted diet
• has ever taken Xyrem / sodium oxybate / GHB at any time
• claustrophobia
• metal implants / objects in the body that may interfere with MRI
• succinic semialdehyde dehydrogenase deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: narcolepsy with cataplexy; patients given single dose of Xyrem	Drug: Xyrem; single 3.0 gram dose; Other Names: Sodium Oxybate; gamma-hydroxybutyrate
Experimental: healthy controls; healthy controls given a single dose of Xyrem	Drug: Xyrem; single 3.0 gram dose; Other Names: Sodium Oxybate; gamma-hydroxybutyrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[C-11]Raclopride BPND at 1 Hour Post Xyrem	BPND (Binding Potential) of [C-11]raclopride measures 1 hour after taking a single 3g dose of Xyrem.	1 hour post Xyrem
% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem	[C-11] raclopride is a radioligand that binds to the D2/3 dopamine receptor in the dopamine-rich striatum and which is sensitive to dopamine occupancy. % change was calculated as follows: (1 hour BPND - baseline BPND)/baseline BPND *100; Mean % change represents the mean of each participant's individual % change within the group.	1 hour post Xyrem
[C-11]Raclopride BPND at 7 Hours Post Xyrem	BPND (Binding Potential) of [C-11]raclopride measures 7 hours after taking a single 3g dose of Xyrem.	7 hours post Xyrem
% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem	[C-11] raclopride is a radioligand that binds to the D2/3 dopamine receptor in the dopamine-rich striatum and which is sensitive to dopamine occupancy. % change was calculated as follows: (7 hours BPND - baseline BPND)/baseline BPND *100; Mean % change represents the mean of each participant's individual % change within the group.	7 hours post Xyrem

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[C-11]DTBZ BPND at 5 Hours Post Xyrem	Measurement of [C-11]DTBZ 5 hours after taking a single dose of 3g Xyrem	5 hours post single Xyrem dose
% Change in PET [C-11] Dihydrotetrabenazine (DTBZ) Binding From Baseline to Five Hours Post Xyrem	[C-11] DTBZ is a radioligand that binds to the vesicular monoamine transporter and which is sensitive to dopamine occupancy. % change was calculated as follows: (5 hour BPND - baseline BPND)/baseline BPND *100; Mean % change represents the mean of each participant's individual % change within the group.	5 hours post single Xyrem dose
Blood Gamma-hydroxybutyrate (GHB) Concentration (AUC)	The concentration of gammahydroxybutyrate in blood of participants who have received a single dose of Xyrem, as measured by Area Under the Curve.	multiple time points from 0 to 7 hours post-Xyrem
Blood Gamma-hydroxybutyrate (GHB) Cmax	The concentration of gammahydroxybutyrate in blood of participants who have received a single dose of Xyrem as measured by Cmax.	multiple time points from 0 to 7 hours post-Xyrem
Duration of Drowsiness	Period of time when the participant was experiencing the sedative action of Xyrem. Data derived from self-report as well as anesthesiologist observation.	observed after receiving single dose of Xyrem, up to 9 hours

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Stephen J Kish, Ph.D., Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): January 23, 2020
• Study Completion (Actual): January 23, 2020

Study Registration Dates

• First Submitted: December 17, 2015
• First Submitted That Met QC Criteria: December 18, 2015
• First Posted (Estimate): December 22, 2015

Study Record Updates

• Last Update Posted (Actual): March 23, 2021
• Last Update Submitted That Met QC Criteria: February 26, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: positron emission tomography; dopamine; Xyrem; narcolepsy with cataplexy
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Disorders of Excessive Somnolence; Narcolepsy; Cataplexy; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Adjuvants, Anesthesia; Sodium Oxybate
• Other Study ID Numbers: 017-2014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes