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Xyrem and Brain Dopamine in Narcolepsy

Primary Purpose

Narcolepsy With Cataplexy, Healthy Controls

Status

Completed

Phase

Phase 4

Locations

Canada

Study Type

Interventional

Intervention

Xyrem

About this trial

This is an interventional basic science trial for Narcolepsy With Cataplexy focused on measuring Xyrem, narcolepsy with cataplexy, positron emission tomography, dopamine

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Centre for Addiction and Mental Health (CAMH)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

narcolepsy with cataplexy

healthy controls

Arm Description

patients given single dose of Xyrem

healthy controls given a single dose of Xyrem

Outcomes

Primary Outcome Measures

[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.

% 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.

[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.

% 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.

Secondary Outcome Measures

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

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

[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)

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

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.

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.

Full Information

NCT ID

NCT02637076

First Posted

December 17, 2015

Last Updated

February 26, 2021

Sponsor

Centre for Addiction and Mental Health

1. Study Identification

Unique Protocol Identification Number

NCT02637076

Brief Title

Xyrem and Brain Dopamine in Narcolepsy

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

January 2016 (undefined)

Primary Completion Date

January 23, 2020 (Actual)

Study Completion Date

January 23, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Centre for Addiction and Mental Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Narcolepsy With Cataplexy, Healthy Controls

Keywords

Xyrem, narcolepsy with cataplexy, positron emission tomography, dopamine

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

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)

Allocation

Non-Randomized

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

narcolepsy with cataplexy

Arm Type

Experimental

Arm Description

patients given single dose of Xyrem

Arm Title

healthy controls

Arm Type

Experimental

Arm Description

healthy controls given a single dose of Xyrem

Intervention Type

Drug

Intervention Name(s)

Xyrem

Other Intervention Name(s)

Sodium Oxybate, gamma-hydroxybutyrate

Intervention Description

single 3.0 gram dose

Primary Outcome Measure Information:

Title

[C-11]Raclopride BPND at 1 Hour Post Xyrem

Description

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

Time Frame

1 hour post Xyrem

Title

% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem

Description

Time Frame

1 hour post Xyrem

Title

[C-11]Raclopride BPND at 7 Hours Post Xyrem

Description

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

Time Frame

7 hours post Xyrem

Title

% Change in PET [C11]Raclopride Binding From Baseline After Single Dose of Xyrem

Description

[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.

Time Frame

7 hours post Xyrem

Secondary Outcome Measure Information:

Title

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

Description

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

Time Frame

5 hours post single Xyrem dose

Title

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

Description

Time Frame

5 hours post single Xyrem dose

Title

Blood Gamma-hydroxybutyrate (GHB) Concentration (AUC)

Description

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

Time Frame

multiple time points from 0 to 7 hours post-Xyrem

Title

Blood Gamma-hydroxybutyrate (GHB) Cmax

Description

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

Time Frame

multiple time points from 0 to 7 hours post-Xyrem

Title

Duration of Drowsiness

Description

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

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephen J Kish, Ph.D.

Organizational Affiliation

Centre for Addiction and Mental Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre for Addiction and Mental Health (CAMH)

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5T 1R8

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

Xyrem and Brain Dopamine in Narcolepsy

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