Xyrem and Brain Dopamine in Narcolepsy

Study Overview
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Brief Summary
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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.

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

Conditions
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Narcolepsy With Cataplexy, Healthy Controls

Intervention / Treatment
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* Drug: Xyrem


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be recruited to fill 2 separate study groups: 1) participants with a diagnosis of narcolepsy with cataplexy; 2) healthy controls.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: narcolepsy with cataplexy<br>patients given single dose of Xyrem | Drug: Xyrem<br>* single 3.0 gram dose<br>* Other names: gamma-hydroxybutyrate;|
| Experimental: healthy controls<br>healthy controls given a single dose of Xyrem | Drug: Xyrem<br>* single 3.0 gram dose<br>* Other names: gamma-hydroxybutyrate;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dopamine, Xyrem, narcolepsy with cataplexy, positron emission tomography