Xyrem and Brain Dopamine in Narcolepsy

Phase 4

Completed

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
narcolepsy with cataplexy	Xyrem	patients given single dose of Xyrem
healthy controls	Xyrem	healthy controls given a single dose of Xyrem

Primary Outcome Measures

Name	Time	Method
% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem	7 hours post 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.
[C-11]Raclopride BPND at 7 Hours Post Xyrem	7 hours post Xyrem	BPND (Binding Potential) of \[C-11\]raclopride measures 7 hours after taking a single 3g dose of Xyrem.
[C-11]Raclopride BPND at 1 Hour Post Xyrem	1 hour post Xyrem	BPND (Binding Potential) of \[C-11\]raclopride measures 1 hour after taking a single 3g dose of Xyrem.

Secondary Outcome Measures

Name	Time	Method
Blood Gamma-hydroxybutyrate (GHB) Cmax	multiple time points from 0 to 7 hours post-Xyrem	The concentration of gammahydroxybutyrate in blood of participants who have received a single dose of Xyrem as measured by Cmax.
Duration of Drowsiness	observed after receiving single dose of Xyrem, up to 9 hours	Period of time when the participant was experiencing the sedative action of Xyrem. Data derived from self-report as well as anesthesiologist observation.
[C-11]DTBZ BPND at 5 Hours Post Xyrem	5 hours post single Xyrem dose	Measurement of \[C-11\]DTBZ 5 hours after taking a single dose of 3g Xyrem
% Change in PET [C-11] Dihydrotetrabenazine (DTBZ) Binding From Baseline to Five Hours Post Xyrem	5 hours post single Xyrem dose	\[C-11\] 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.
Blood Gamma-hydroxybutyrate (GHB) Concentration (AUC)	multiple time points from 0 to 7 hours post-Xyrem	The concentration of gammahydroxybutyrate in blood of participants who have received a single dose of Xyrem, as measured by Area Under the Curve.

Locations (1): Centre for Addiction and Mental Health (CAMH)
🇨🇦
Toronto, Ontario, Canada
Centre for Addiction and Mental Health (CAMH)
🇨🇦Toronto, Ontario, Canada