Xyrem and Brain Dopamine in Narcolepsy

NCT02637076 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 017-2014
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Narcolepsy With Cataplexy; Healthy Controls

Keywords

Xyrem; narcolepsy with cataplexy; positron emission tomography; dopamine

Outcome Measures

Primary Outcomes (4)

• [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 Outcomes (5)

• [C-11]DTBZ BPND at 5 Hours Post Xyrem

  5 hours post single Xyrem dose

• % Change in PET [C-11] Dihydrotetrabenazine (DTBZ) Binding From Baseline to Five Hours Post Xyrem

  5 hours post single Xyrem dose

• Blood Gamma-hydroxybutyrate (GHB) Concentration (AUC)

  multiple time points from 0 to 7 hours post-Xyrem

• Blood Gamma-hydroxybutyrate (GHB) Cmax

  multiple time points from 0 to 7 hours post-Xyrem

• Duration of Drowsiness

  observed after receiving single dose of Xyrem, up to 9 hours

Study Arms (2)

narcolepsy with cataplexy

EXPERIMENTAL

patients given single dose of Xyrem

Drug: Xyrem

healthy controls

EXPERIMENTAL

healthy controls given a single dose of Xyrem

Drug: Xyrem

Interventions

Xyrem DRUG

single 3.0 gram dose

Also known as: Sodium Oxybate, gamma-hydroxybutyrate

healthy controls; narcolepsy with cataplexy

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• current diagnosis of narcolepsy with cataplexy OR healthy control

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health (CAMH)

Toronto, Ontario, M5T 1R8, Canada

Location

MeSH Terms

Conditions

Narcolepsy

Interventions

Sodium Oxybate

Condition Hierarchy (Ancestors)

Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Hydroxybutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids

Results Point of Contact

• Title: Dr. Stephen Kish
• Organization: CAMH

stephen.kish@utoronto.ca

416-535-8501

Study Officials

• Stephen J Kish, Ph.D.

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist, Head Human Brain Lab

Model Details: Participants will be recruited to fill 2 separate study groups: 1) participants with a diagnosis of narcolepsy with cataplexy; 2) healthy controls.

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: December 22, 2015
• Study Start: January 1, 2016
• Primary Completion: January 23, 2020
• Study Completion: January 23, 2020
• Last Updated: March 23, 2021
• Results First Posted: March 23, 2021

Record last verified: 2021-02

Locations

CA (1)