Blinded, Randomized Study of Gabapentin (Neurontin®) and Gabapentin Enacarbil (Horizant™) in Restless Leg Syndrome

The study will compare the safety, effectiveness and tolerability of gabapentin (Neurontin) versus gabapentin enacarbil (Horizant) as treatment restless leg syndrome.

Study Overview

• Status: Terminated
• Conditions: Restless Leg Syndrome
• Intervention / Treatment: Drug: Gabapentin immediate release; Drug: Gabapentin enacarbil extended release

Detailed Description

The study will compare the safety, effectiveness and tolerability of gabapentin (Neurontin) versus gabapentin enacarbil (Horizant) as treatment restless leg syndrome. Subjects will be randomized to gabapentin (IR) or Horizant™ (ER). Dosing will be blinded to both patient and study team members. Once study medication dosing has been optimized, subjects will then remain on a stable dose for six weeks until study endpoint, after which subjects will be down-titrated off of study medications.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Outpatients with a diagnosis of primary restless leg syndrome using the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria8.
2. RLS symptoms ≥ 15 nights of the month prior to study enrollment and for ≥ 4 of 7 consecutive nights in the week prior to study enrollment (if untreated).
3. Age 18 years to 80 years.
4. International Restless Legs Scale (IRLS) Total severity score of ≥ 15 (moderate to severe severity). 8
5. Had significant sleep disturbance on item 4 of IRLS.8
6. Women of child-bearing potential must use a reliable method of contraception.
7. Informed consent. Subject must be willing and able to complete all study procedures.

Exclusion Criteria:

1. Any illness that in the investigator's opinion preclude participation in this study.
2. Subjects with non-RLS-related sleep disorders (e.g., sleep apnea)
3. Subjects with neurological diseases or movement disorders other than RLS (e.g., diabetic neuropathy, Parkinson's disease, multiple sclerosis, dyskinesias, and dystonias)
4. Pregnancy or lactation.
5. Concurrent participation in another clinical study.
6. Dementia or other psychiatric illness that prevents the patient from giving informed consent (Mini-Mental State Examination scores less than 27).
7. Legal incapacity or limited legal capacity.
8. History of RLS symptom augmentation or early-morning rebound with previous dopamine-agonist treatment.
9. Clinically significant abnormalities in renal function. 3,8,10
10. Presence of severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease.
11. Concomitant treatment with drugs known to affect sleep/wake, RLS or periodic limb movements, including antidepressants. Subjects receiving treatment for RLS at screening will be required to discontinue and wash out for a minimum of 5 half-lives.
12. Body mass index greater than 34 kg/m2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: gabapentin immediate release; Gabapentin IR is the immediate release form of the medication. Subjects randomized to gabapentin IR will be started out at a dose of 300mg per day, taken one hour before bedtime for the first week. Daily dose will be increased by 300 mg daily every 4 days until 1200 mg of gabapentin IR is reached or until a stable, tolerated dose of gabapentin IR that relieves symptoms has been maintained for 2 weeks (IRLS scores less than 15). Those patients who cannot tolerate gabapentin IR will be allowed to down titrate by one dose level (300 mg daily), before dropping out of the study.	Drug: Gabapentin immediate release; up to 1200 mg per day; Other Names: Neurontin
Active Comparator: gabapentin enacarbil extended release; Horizant is the extended release form of gabapentin enacarbil. Subjects randomized to Horizant will take 600mg at 5 pm. After four days of stable dosing of Horizant, subjects in this study group will be evaluated by phone for changes in RLS symptoms and Patient Global Impression scale to determine if a dose increase is warranted. Subjects in this group may be titrated up to 1200 mg daily during the 2 week titration period.	Drug: Gabapentin enacarbil extended release; up to 1200 mg per day; Other Names: Horizant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
International Restless Leg Syndrome Rating Scale (IRLS)	The IRLS is a measure of severity of Restless Legs Syndrome. It includes 10 items, measured on a scale of 0-4. A score of 1-10 indicates mild severity, 11-20 indicates moderate severity, 21-30 is severe and 31-40 is very severe. Primary outcome is the difference in IRLS scores for each of the treatment regimens. from 0 to 4.	10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Restless Leg Syndrome Quality of Life Scale (RLSQoL)	The Restless Legs Syndrome Quality of Life questionnaire (RLSQoL) assesses the impact of RLS on daily life, emotional well-being, social life, and work life.	Baseline, day 35, day 54.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medical Outcomes Study (MOS) Sleep Scale	The MOS Sleep Scale consists of 12 individual items (4 sleep disturbance, 2 sleep adequacy, 1 quantity of sleep and optimal sleep, 3 somnolence, 1 snoring, and 1 shortness of breath) and takes 5 to 10 minutes to complete. Question 1 is scored on a scale of 1 to 5 ( 1 = 0-15 min to more than 60 min) and Questions 2 to 12 are scored on a scale of 1 to 6 (1 = all of the time to 6 = none of the time. The Sleep Disturbance Subscale score is derived from the scores to Questions 1, 3, 7, and 8 and ranges from 0 to 100, where higher scores indicate greater sleep disturbance.	Baseline, day 35, day 54

Collaborators and Investigators

• Sponsor: Theresa Zesiewicz, MD
• Investigators: Principal Investigator: Theresa Zesiewicz, MD, FAAN, University of South Florida

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: April 15, 2014
• First Submitted That Met QC Criteria: April 15, 2014
• First Posted (Estimate): April 17, 2014

Study Record Updates

• Last Update Posted (Actual): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 8, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: gabapentin; Neurontin; RLS; Restless leg syndrome; gabapentin enacarbil; Horizant
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Dyskinesias; Psychomotor Disorders; Parasomnias; Syndrome; Psychomotor Agitation; Restless Legs Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin
• Other Study ID Numbers: RLS and Gabapentin or Horizant