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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| narcolepsy with cataplexy | Experimental | patients given single dose of Xyrem |
|
| healthy controls | Experimental | healthy controls given a single dose of Xyrem |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Xyrem | Drug | single 3.0 gram dose |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen J Kish, Ph.D. | Centre for Addiction and Mental Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Addiction and Mental Health (CAMH) | Toronto | Ontario | M5T 1R8 | Canada |
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| ID | Title | Description |
|---|---|---|
| FG000 | Narcolepsy With Cataplexy | patients given single dose of Xyrem Xyrem: single 3.0 gram dose |
| FG001 | Healthy Controls | healthy controls given a single dose of Xyrem Xyrem: single 3.0 gram dose |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Narcolepsy With Cataplexy | patients given single dose of Xyrem Xyrem: single 3.0 gram dose |
| BG001 | Healthy Controls | healthy controls given a single dose of Xyrem Xyrem: single 3.0 gram dose |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | BPND (Binding Potential) | 1 hour post Xyrem |
|
|
Adverse events will be assessed at each study visit following administration of the first PET radiotracer until the follow-up phone after Xyrem administration (2 visits plus 1 follow-up phone call), an average of 10 days per participant.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Narcolepsy With Cataplexy | patients given single dose of Xyrem Xyrem: single 3.0 gram dose |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Euphoria | General disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Stephen Kish | CAMH | 416-535-8501 | 36256 | stephen.kish@utoronto.ca |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 13, 2017 | Jan 25, 2021 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 27, 2019 | Jan 25, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D009290 | Narcolepsy |
| ID | Term |
|---|---|
| D006970 | Disorders of Excessive Somnolence |
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
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| ID | Term |
|---|---|
| D012978 | Sodium Oxybate |
| ID | Term |
|---|---|
| D006885 | Hydroxybutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
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Participants will be recruited to fill 2 separate study groups: 1) participants with a diagnosis of narcolepsy with cataplexy; 2) healthy controls.
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[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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| [C-11]raclopride BPND at Baseline | [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. | Mean | Standard Deviation | BPND (Binding Potential) |
|
| [C-11]DTBZ BPND at Baseline | [C-11] DTBZ is a radioligand that binds to the vesicular monoamine transporter and which is sensitive to dopamine occupancy. | Mean | Standard Deviation | BPND (Binding Potential) |
|
| Counts |
|---|
| Participants |
|
|
|
| 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. | Posted | Mean | Standard Deviation | percentage change from baseline | 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. | Posted | Mean | Standard Deviation | BPND (Binding Potential) | 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. | Posted | Mean | Standard Deviation | percentage change from baseline | 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 | Posted | Mean | Standard Deviation | BPND (binding potential) | 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. | Posted | Mean | Standard Deviation | percentage change from baseline | 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. | Posted | Mean | Standard Deviation | AUC (ug/ml*hr) | 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. | Posted | Mean | Standard Deviation | mg/ml | 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. | Posted | Median | Full Range | minutes | observed after receiving single dose of Xyrem, up to 9 hours |
|
|
|
| 0 |
| 2 |
| 0 |
| 2 |
| 0 |
| 2 |
| EG001 | Healthy Controls | healthy controls given a single dose of Xyrem Xyrem: single 3.0 gram dose | 0 | 15 | 0 | 15 | 4 | 15 |
| Nausea | General disorders | Non-systematic Assessment |
|
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| D009422 | Nervous System Diseases |
| D001523 | Mental Disorders |
| D009930 |
| Organic Chemicals |
| D006880 | Hydroxy Acids |
| Sensorimotor Striatum |
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| Sensorimotor Striatum |
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| Sensorimotor Striatum |
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| Sensorimotor Striatum |
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| Sensorimotor Striatum |
|