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Effects of Gabapentin Enacarbil on Arousals, Heart Rate, Blood Pressure and PLMs in Restless Legs Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02424695
Recruitment Status : Unknown
Verified April 2015 by Mansoor Ahmed M.D., Cleveland Sleep Research Center.
Recruitment status was:  Not yet recruiting
First Posted : April 23, 2015
Last Update Posted : April 23, 2015
XenoPort, Inc.
YRT Limited
Information provided by (Responsible Party):
Mansoor Ahmed M.D., Cleveland Sleep Research Center

Brief Summary:
This is a phase IV single-blind, placebo run-in fixed dose single-group study to assess objective and subjective effects of GEn on sleep EEG, BP, and anterior tibialis EMG responsivity in patients with RLS. The study will include 8 visits over a period of up to 8 weeks for eligible subjects including a 1 to 3-week Screening/Washout Period, a 1-week placebo run-in period, and a 4-week Treatment Period.The first placebo dose will be administered within 1 to 3 weeks after Screening/Washout. The total duration of the study from the first subject enrolled to the last subject completed will be approximately 1 year.

Condition or disease Intervention/treatment Phase
Restless Legs Syndrome Drug: Gabapentin Enacarbil (GEn) Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Effects of Gabapentin Enacarbil on Intensity of Cortical Arousal, Heart Rate, Blood Pressure and Anterior Tibialis EMG Responses Associated With PLMs During Sleep in Patients With RLS Using a Novel Computer Assisted Scoring System
Study Start Date : June 2015
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : July 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Restless Legs

Arm Intervention/treatment
Experimental: Single Gabapentin Enacarbil Arm

Gabapentin Enacarbil (Gen) 600 mg will be administered once daily for 4 weeks

Matching placebo will be administered once daily for one week prior initiation of treatment with GEn

Drug: Gabapentin Enacarbil (GEn)

HORIZANT Extended-Release Tablets containing 600 mg of gabapentin enacarbil are white to off-white, with occasional black/grey spots, oval-shaped tablets debossed with "GS LFG", supplied as:

600 mg: NDC 53451-0101-1.The drug will be stored at 25°C (77°F) (excursions permitted 15° to 30°C (59° to 86°F)) Matching placebo will be provided by Xenoport Inc.

Other Name: HORIZANT

Drug: Placebo

Primary Outcome Measures :
  1. The mean change from baseline to week 4 in intensity of cortical arousals associated with periodic limb movements (PLMs) [ Time Frame: 4 weeks ]
    Cortical EEG arousals will be scored using wavelet analysis of C3/A2 and C4/A1 EEG signals. Arousals scored in NREM sleep will be assigned a score from 0-9. This arousal scaling is entirely subjective. Wavelet analysis will be performed on each of the scaled arousals using wavelet features that correlate with arousal intensity. The arousal intensity will be measured using Wavelet Transform which is superior for analyzing signals such as EEG.

Secondary Outcome Measures :
  1. The mean change from baseline to week 4 in heart rate variability associated with arousals secondary to periodic limb movements (PLMs) [ Time Frame: 4 weeks ]
    Beat to beat heart rate measurement will identify the highest value in the interval 2-12 seconds preceding each arousal which will be used as a baseline heart rate. The highest heart rate in the interval between arousal and at 8 seconds after its end, and the difference from baseline will represent the change in heart rate associated with the arousal.

  2. The mean change from baseline to week 4 in blood pressure associated with arousals secondary to periodic limb movements (PLMs) [ Time Frame: 4 weeks ]
    Blood pressure changes will be identified using the same technique as the heart rate changes. Continuous blood pressure will be monitored using Somnotouch RESP. Using the 2-12 seconds preceding each arousal, any identified change between onset of arousal and at 8 seconds after its end will represent the change in blood pressure.

  3. The mean change from baseline to week 4 in periodic limb movement (PLM) intensity [ Time Frame: 4 weeks ]
    Periodic limb movement (PLM) intensity will be derived by measuring the highest anterior tibialis EMG amplitude during the 2-12 seconds prior to arousal onset and comparing to maximum EMG amplitude during PLMs with or without associated arousal.

  4. The mean change from Baseline to week 4 in Rechtschaffen and Kales polysomnography parameters [ Time Frame: 4 weeks ]
    Polysomnography (PSG) studies will be recorded for 8 hours using standard techniques described by Rechtschaffen and Kales (R&K). The R&K standard PSG parameters include: Total sleep time (TST), wake after sleep onset (WASO), latency to persistent sleep (LPS 10), sleep efficiency (SE), number of awakenings per hour of sleep (Awakenings Index), arousals index (AI), sleep stage percentages, periodic limb movements per hour (PLMI), and periodic limb movements associated with arousal per hour (PLMAI).

  5. The mean change from baseline to week 4 in International Restless Legs Syndrome (IRLS) Rating Scale total score [ Time Frame: 4 weeks ]
  6. The mean change from Baseline to week 4 in proportion of responders ("much"/ "very much" improved) on the investigator-rated Clinical Global Impression-Improvement (CGI-I) scale [ Time Frame: 4 weeks ]
  7. The mean change from Baseline to week 4 in proportion of responders ("moderately better" to "a great deal better") on the patient Global Impression of Change (PGIC) scale [ Time Frame: 4 weeks ]
  8. The mean change from Baseline to week 4 in Post Sleep Questionnaire (PSQ)scores [ Time Frame: 4 weeks ]
  9. The mean change from Baseline to week 4 in Subjective Sleep Questionnaire (SSQ) scores [ Time Frame: 4 weeks ]
  10. The mean change from Baseline to week 4 in Restless Legs Syndrome Quality of Life Questionnaire (RLSQoL) scores [ Time Frame: 4 weeks ]
  11. The mean change from Baseline to week 4 in Restless Legs Syndrome- Next Day Impact Questionnaire (RLS-NDI) scores [ Time Frame: 4 weeks ]
  12. The mean change from Baseline to week 4 in the Epworth Sleepiness Scale (ESS) scores [ Time Frame: 4 weeks ]
  13. Number of subjects with treatment emergent adverse events [ Time Frame: 4 weeks ]
  14. Number of subjects with mild, moderate and severe adverse events [ Time Frame: 4 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female subjects ages 18 to 65 years with a diagnosis of primary moderate to severe RLS
  2. A minimum of 6-month history of RLS symptoms
  3. IRLS score >15 points (at visits 1 and 2) and a score of > 2 on item 4
  4. RLS symptoms on at least 15 days during the month prior to screening (or if on treatment, similar symptom frequency before the start of treatment)
  5. RLS symptoms for >4 out of 7 evenings /day during the week prior to screening
  6. History of sleep disturbance due to RLS over the last 3 months
  7. Subjective history of WASO ≥ 60 min; TST < 6.5 hours; subjective sleep latency ≥ 30 min on at least 3 nights per week within the last 3 months
  8. Subjective complaint of WASO ≥ 60 min; TST< 6.5 hours; subjective sleep latency ≥ 30 min on at least 3 nights out of 7on the SSQ during the 1 week prior to Visit 2
  9. Objective WASO of ≥30 minutes, TST < 6.5 hours and PLMI ≥ 10 during adaptation in baseline PSG 1
  10. Females of child bearing potential willing to use birth control
  11. Subject can read understand and sign consent form
  12. Subject able to complete the study and to comply with study instructions and procedures

Exclusion Criteria:

  1. Subject has an apnea-hypopnea index of ≥10/ hour during adaptation/baseline night PSGs. Subjects with OSA controlled by CPAP will be accepted
  2. Evidence of secondary RLS
  3. Subject has any of the following medical conditions, laboratory abnormalities or disorders:

    Hepatic impairment Impaired renal function or renal dysfunction requiring hemodialysis; Serum ferritin level <20 mcg/L (ng/mL)

  4. Clinically significant ECG abnormalities
  5. Any unstable medical condition that could impact subject's safety and study outcomes
  6. Uncontrolled hypertension at Screening or at time of treatment initiation
  7. Subjects diagnosed with additional sleep disorders other than RLS-associated sleep disturbance
  8. Neurologic disease or movement disorder, rheumatoid arthritis, fibromyalgia, uncontrolled psychiatric illness, current diagnosis or history of epilepsy or seizure disorder
  9. Chronic hepatitis B or hepatitis C
  10. Subject currently suffering from moderate or severe depression
  11. Subject unable to discontinue prohibited medications during the Screening period and throughout the duration of the study.
  12. Subject has consumed food or beverages containing more than 400 mg of caffeine or other xanthines (e.g., coffee, cola, tea, chocolate) per day over the preceding month prior to Screening or unwilling to refrain from consuming any caffeinated food or beverage within 8 hours prior to any PSG assessment.
  13. Subject has typical consumption of >14 alcoholic units in any week, or more than 5 alcoholic units in any single day, over the month preceding the Screening visit or unwilling to refrain from consuming alcohol within 24 hours of any PSG assessment
  14. Night workers, shift workers or any others whose sleeping habits are incompatible with the study design, or who would be required to make significant changes to their bedtime during the course of the study
  15. Subject who might be non-compliant with the visit schedule, procedures, or medication administration
  16. Subject is a pregnant or nursing female
  17. A history of allergy or medically significant adverse reaction or intolerance to gabapentin or GEn
  18. A history of alcohol, narcotic, benzodiazepine, or other substance abuse or dependence within the past year
  19. A history of augmentation or early morning rebound of RLS symptoms without a history of prior response to treatment.
  20. Subject has received previous treatment with levodopa/carbidopa, dopamine agonists, pregabalin, gabapentin or GEn in the 3 weeks prior to Visit
  21. Subject has received` other treatments for RLS (e.g., opioids, benzodiazepines) at least 2 weeks prior to Visit 2
  22. Participation in any clinical drug or device trial within 30 days prior to Baseline

Information from the National Library of Medicine

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 identifier (NCT number): NCT02424695

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Contact: Rozina Aamir, MS, MBA 440-243-8044
Contact: Zahra A Jishi, MPH 440-243-8044

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United States, Ohio
Cleveland Sleep Research Center
Middleburg Heights, Ohio, United States, 44130
Sponsors and Collaborators
Cleveland Sleep Research Center
XenoPort, Inc.
YRT Limited
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Principal Investigator: Mansoor Ahmed, MD Cleveland Sleep Research Center

Publications of Results:
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Responsible Party: Mansoor Ahmed M.D., Medical Director, Cleveland Sleep Research Center Identifier: NCT02424695    
Other Study ID Numbers: XP-IIT-0031
First Posted: April 23, 2015    Key Record Dates
Last Update Posted: April 23, 2015
Last Verified: April 2015
Keywords provided by Mansoor Ahmed M.D., Cleveland Sleep Research Center:
Cortical arousal intensity
Heart rate
Blood pressure
Additional relevant MeSH terms:
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Psychomotor Agitation
Restless Legs Syndrome
Pathologic Processes
Neurologic Manifestations
Nervous System Diseases
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Mental Disorders
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action