Altered Brain GABA and Glutamate in Restless Legs Syndrome (RLS)
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|ClinicalTrials.gov Identifier: NCT01109537|
Recruitment Status : Completed
First Posted : April 23, 2010
Last Update Posted : January 7, 2015
|Condition or disease|
|Restless Legs Syndrome|
Hide Detailed Description
The study will involve a screening visit, a washout period for those taking RLS medications, a night of actigraphy, an overnight polysomnogram, an MRI scan, and an MRS scan. The polysomnography and MR scan visits will occur on consecutive days.
Visit 1: Screening Visit
The informed consent process for the study will be completed and a signed informed consent form will be obtained. All subjects with RLS will undergo a clinical interview in order to confirm or exclude an RLS diagnosis consistent with the International Restless Legs Syndrome Study Group criteria and to determine the presence of any psychiatric or medical disorders. The following study assessments will be completed:
- International Restless Legs Syndrome Scale (IRLS) (RLS subjects only)
- Clinical Global Impression-Severity (CGI) (RLS subjects only)
- Insomnia Severity Index (ISI)
- Beck Depression Inventory
- Pittsburgh Sleep Quality Index (PSQI)
- Hamilton Anxiety Scale (HAM-A)
- Sleep Health Centers Questionnaire
- Metal implant questionnaire
All women will have a urine pregnancy test and all subjects will have a urine sample for drug screening collected.
Subjects in the RLS group will be required to discontinue their RLS medications at least 48 hours prior to the PSG.
An actigraph will be used to record limb movements of both legs the night before the PSG. The actigraph will be worn from the subjects' bedtime until the subjects' final wake time Subjects will also record their bedtime and wake time on the Actigraphy Data Form. Data from the night of actigraphy will be used to monitor subjects' sleep.
Visit 2: Polysomnography (PSG) The PSG will occur on the night prior to the MRS visit. The time of lights out during all PSG sessions will be determined for each subject based on self report of usual bedtime.
Channels will include an electroencephalograph (EEG), an electro-oculogram (EOG), a submental electromyography (EMG), EMG of both anterior tibialis muscles (separate channels for each leg), oral/nasal airflow, pulse oximetry, and respiratory effort. The PSG will be analyzed for traditional sleep staging. Measures from the PSG will include Sleep Onset Latency (SOL), Wake After Sleep Onset (WASO), Sleep Efficiency (SE), N-REM and REM percentages, Periodic Limb Movement Index (PLMI) and PLMs associated with arousal per hour of sleep (PLMAI).
Visit 3: MR scans
Following visits 1 and 2, qualified subjects will undergo Magnetic Resonance brain scans the Brain Imaging Center of McLean Hospital in Belmont, MA. Prior to MR scanning, subjects will be questioned for a second time about the presence of metallic implants and fragments or any other contraindications to MR imaging. They will be asked about recent alcohol, drug (licit and illicit), and caffeine use. They will also be asked to provide a urine sample for drug screening. Women will take a urine pregnancy test. Also, since brain GABA levels can be affected by the menstrual cycle, women will be scheduled to have their MR scans during the first portion of their menstrual cycle. Subjects will also be asked to complete the following assessments before the MR scans:
- IRLS (modified)
- Medical Outcomes Study Sleep Scale (modified) (MOS)
- Profile of Mood States (POMS)
- Patient Global Impression-Severity (PGI-S)
- State Trait Anxiety Inventory (STAI)
Subjects will undergo proton magnetic resonance spectroscopy (MRS) at 4T. In addition, in accordance with the McLean Hospital Neuroimaging center guidelines, subjects will additionally have a MR screening scan at either 1.5T or 3T. All MR recordings will be obtained using parameters that are within FDA safety guidelines for exposure to static magnetic fields, radio-frequency energy deposition, magnetic field switching rates and acoustic noise levels. GABA and glutamate levels will be derived from MRS Scan at 4T. Subjects will be in each scanner for approximately one hour. At the conclusion of each scan, subjects will be queried regarding any adverse effects related to MR scans. The subject will have completed the study at the conclusion of the MR scans.
During the MRS at 4T, patients will complete a modified Suggested Immobilization Test (SIT). During the SIT, the subjects will be asked by study staff to verbally rate the level of discomfort in their legs on a scale from 1 (no discomfort) to 10 (extreme discomfort). Subjects will be asked to make a rating in five minute intervals over one hour.
In the case that MR scans on the 1.5T/3T and 4T MR scanners cannot be coordinated on the same visit day at the McLean Brain Imaging center due to scheduling conflicts, the subject will be offered the opportunity to return to McLean to have the remaining scan on a separate day. Subjects will still be offered $50 for completion of each scan. Also, in the case that the data collected during MR imaging is not usable (due to technical problems with the scanner, excessive noise in the measurement, etc.), the subject may be contacted and offered a repeat MRS scan on a separate date. Subjects will be compensated an additional $100 for completion of such a repeat MRS scan.
The Primary Endpoints of this protocol are regional GABA and glutamate levels derived from 4T MRS.
|Study Type :||Observational|
|Actual Enrollment :||75 participants|
|Observational Model:||Case Control|
|Official Title:||Thalamic and Anterior Cingulate Cortex GABA and Glutamate in Restless Legs Syndrome: A 1-HMRS Study|
|Study Start Date :||April 2010|
|Actual Primary Completion Date :||May 2014|
|Actual Study Completion Date :||May 2014|
- Regional GABA and glutamate levels derived from 4T MRS. [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01109537
|United States, Massachusetts|
|Brighton, Massachusetts, United States, 02135|
|Principal Investigator:||John W Winkelman, MD, PhD||Sleep Health Centers, Brigham and Women's Hospital|