Xyrem and Brain Dopamine in Narcolepsy

Healthy Controls Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02637076
• Other study ID #: 017-2014
• Status: Completed
• Phase: Phase 4
• Start date: January 2016
• Est. completion date: January 23, 2020

Study information

• Verified date: February 2021
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: January 23, 2020
• Est. primary completion date: January 23, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cataplexy
• Healthy Controls
• Narcolepsy
• Narcolepsy With Cataplexy

Intervention

Drug:
• Xyrem
single 3.0 gram dose

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health (CAMH)	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[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
Primary	% 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
Primary	[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
Primary	% 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	[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
Secondary	% 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
Secondary	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
Secondary	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
Secondary	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