Xyrem and Brain Dopamine in Narcolepsy

GHB

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.

Intervention / Treatment

Participants will be recruited to fill 2 separate study groups: 1) participants with a diagnosis of narcolepsy with cataplexy; 2) healthy controls.
  • Xyrem (DRUG)
    single 3.0 gram dose

Condition or Disease

  • Narcolepsy With Cataplexy
  • Healthy Controls

Phase

  • Phase 4

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 19 Years and older   (Adult, Older Adult)
    Enrollment: 17 (ACTUAL)
    Funded by: Other
    Allocation: Non-Randomized
    Primary Purpose: Basic Science

    Masking

    Clinical Trial Dates

    Start date: Jan 01, 2016
    Primary Completion: Jan 23, 2020 ACTUAL
    Completion Date: Jan 23, 2020 ACTUAL
    Study First Posted: Dec 22, 2015 ESTIMATED
    Results First Posted: Mar 23, 2021 ACTUAL
    Last Updated: Feb 26, 2021

    Sponsors / Collaborators

    Lead Sponsor: Centre for Addiction and Mental Health
    Responsible Party: N/A

    Location

    Toronto, Ontario, Canada

    Participant Groups

    • patients given single dose of Xyrem

    • healthy controls given a single dose of Xyrem

    Eligibility Criteria

    Sex: All
    Minimum Age: 19
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    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

    Primary Outcomes

    • BPND (Binding Potential) of \[C-11\]raclopride measures 1 hour after taking a single 3g 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.

    • BPND (Binding Potential) of \[C-11\]raclopride measures 7 hours after taking a single 3g 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.

    Secondary Outcomes

    • Measurement of \[C-11\]DTBZ 5 hours after taking a single dose of 3g 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.

    • The concentration of gammahydroxybutyrate in blood of participants who have received a single dose of Xyrem, as measured by Area Under the Curve.

    • The concentration of gammahydroxybutyrate in blood of participants who have received a single dose of Xyrem as measured by Cmax.

    • Period of time when the participant was experiencing the sedative action of Xyrem. Data derived from self-report as well as anesthesiologist observation.

    More Details

    NCT Number: NCT02637076
    Other IDs: 017-2014
    Study URL: https://clinicaltrials.gov/study/NCT02637076
    Last updated: Sep 29, 2023