The Effects Of Ropinirole On Mood Or Mild Depression In Patients With Moderate To Severe Restless Legs Syndrome

A Multicenter 3:1-randomized Placebo-controlled Double-blind Phase IIIb Study on the Effects of Ropinirole on Mood/(Subclinical) Depression in the Therapy of Patients With Moderate to Severe Idiopathic RLS in Germany

Ropinirole has shown to improve mood in depressed patients as well as to improve the symptoms of Restless Legs Syndrome. Up to 40% of RLS patients suffer from mild depression, therefore it would be important for decisions no therapy to know whether a drug could improve both depressive and RLS symptoms.

Study Overview

• Status: Completed
• Conditions: Restless Legs Syndrome; Moderate to Severe Idiopathic Restless Legs Syndrome (RLS)
• Intervention / Treatment: Drug: Ropinirole

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • GSK Investigational Site
  • Berlin, Germany, 10629
    • GSK Investigational Site
  • Berlin, Germany, 10787
    • GSK Investigational Site
  • Berlin, Germany, 10969
    • GSK Investigational Site
  • Berlin, Germany, 10625
    • GSK Investigational Site
  • Berlin, Germany, 12167
    • GSK Investigational Site
  • Berlin, Germany, 13156
    • GSK Investigational Site
  • Berlin, Germany, 13053
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Ellwangen, Baden-Wuerttemberg, Germany, 73479
      • GSK Investigational Site
    • Freiburg, Baden-Wuerttemberg, Germany, 79104
      • GSK Investigational Site
    • Ostfildern, Baden-Wuerttemberg, Germany, 73760
      • GSK Investigational Site
    • Ulm, Baden-Wuerttemberg, Germany, 89081
      • GSK Investigational Site
    • Ulm, Baden-Wuerttemberg, Germany, 89073
      • GSK Investigational Site
  • Bayern
    • Muenchen, Bayern, Germany, 80331
      • GSK Investigational Site
    • Nuernberg, Bayern, Germany, 90403
      • GSK Investigational Site
    • Regensburg, Bayern, Germany, 93053
      • GSK Investigational Site
    • Unterhaching, Bayern, Germany, 82008
      • GSK Investigational Site
    • Wuerzburg, Bayern, Germany, 97070
      • GSK Investigational Site
  • Brandenburg
    • Bad Saarow, Brandenburg, Germany, 15526
      • GSK Investigational Site
  • Hessen
    • Bad Homburg, Hessen, Germany, 61348
      • GSK Investigational Site
    • Butzbach, Hessen, Germany, 35510
      • GSK Investigational Site
    • Herborn, Hessen, Germany, 35745
      • GSK Investigational Site
    • Kassel, Hessen, Germany, 34128
      • GSK Investigational Site
  • Mecklenburg-Vorpommern
    • Anklam, Mecklenburg-Vorpommern, Germany, 17389
      • GSK Investigational Site
    • Schwerin, Mecklenburg-Vorpommern, Germany, 19053
      • GSK Investigational Site
    • Wismar, Mecklenburg-Vorpommern, Germany, 23966
      • GSK Investigational Site
  • Niedersachsen
    • Achim, Niedersachsen, Germany, 28832
      • GSK Investigational Site
    • Goettingen, Niedersachsen, Germany, 37075
      • GSK Investigational Site
    • Goettingen, Niedersachsen, Germany, 37073
      • GSK Investigational Site
    • Hildesheim, Niedersachsen, Germany, 31134
      • GSK Investigational Site
    • Wolfsburg, Niedersachsen, Germany, 38440
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Bielefeld, Nordrhein-Westfalen, Germany, 33647
      • GSK Investigational Site
    • Bochum, Nordrhein-Westfalen, Germany, 44787
      • GSK Investigational Site
    • Bochum, Nordrhein-Westfalen, Germany, 44791
      • GSK Investigational Site
    • Bochum, Nordrhein-Westfalen, Germany, 44805
      • GSK Investigational Site
    • Bochum, Nordrhein-Westfalen, Germany, 44809
      • GSK Investigational Site
    • Bochum, Nordrhein-Westfalen, Germany, 44892
      • GSK Investigational Site
    • Dueren, Nordrhein-Westfalen, Germany, 52349
      • GSK Investigational Site
    • Duesseldorf, Nordrhein-Westfalen, Germany, 40212
      • GSK Investigational Site
    • Gelsenkirchen, Nordrhein-Westfalen, Germany, 45879
      • GSK Investigational Site
    • Guetersloh, Nordrhein-Westfalen, Germany, 33330
      • GSK Investigational Site
    • Hattingen, Nordrhein-Westfalen, Germany, 45525
      • GSK Investigational Site
    • Juelich, Nordrhein-Westfalen, Germany, 52428
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Limburgerhof, Rheinland-Pfalz, Germany, 67117
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • GSK Investigational Site
  • Sachsen-Anhalt
    • Halle, Sachsen-Anhalt, Germany, 06118
      • GSK Investigational Site
    • Koethen, Sachsen-Anhalt, Germany, 06366
      • GSK Investigational Site
  • Schleswig-Holstein
    • Oldenburg, Schleswig-Holstein, Germany, 26122
      • GSK Investigational Site
  • Thueringen
    • Gera, Thueringen, Germany, 07551
      • GSK Investigational Site
    • Jena, Thueringen, Germany, 07743
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• diagnosis of idiopathic Restless Legs Syndrome, confirmed by a score of at least 11 on the RLS Diagnostic Index
• certain severity of symptoms (at least score of 15 on the International Restless Legs Score (IRLS)
• Have had RLS symptoms for at least 15 nights in the last four weeks.
• < 6 hours of sleep in nights with RLS symptoms
• MADRS (depression rating scale) score of at least 12 (= borderline to depression) at baseline

Exclusion criteria:

• any other sleep disorder that might interfere with the RLS symptoms or sleep (e.g. sleep apnea disorder, narcolepsy)
• Secondary RLS due to diagnosis of renal insufficiency, polyneuropathy, pregnancy (see below), iron deficiency anemia
• Any significant psychiatric disorders (e.g. schizophrenia, bipolar disorder); depression which by judgement of the investigator is caused by RLS, is not an exclusion criterion.
• Current or past suicidality
• medication known to trigger/aggravate/ cause or interfere with RLS symptoms (e.g. most antidepressants, lithium, neuroleptics, opioids, carbidopa, clonidine, antihistamines, anticonvulsants etc.).
• daytime RLS symptoms which require treatment (daytime: 10 a.m. until 6 p.m.).
• concomitant movement disorders (e.g. Parkinson's Disease, dyskinesia, dystonia).
• medical conditions with symptoms which could affect assessments of efficacy (e.g. diabetes, rheumatoid arthritis, fibromyalgia syndrome, cancer etc.).
• Subjects taking any medication known to induce drowsiness or to affect sleep.
• Subjects who are pregnant, lactating or of childbearing potential. Women of childbearing potential must use adequate contraception
• clinically significant or unstable medical conditions (e.g. severe heart disease, severe liver or kidney disease etc.).
• pain syndromes, caused by other disorders than RLS
• excessive caffeine intake
• diastolic blood pressure >110mmHg or <50mmHg or systolic blood pressure >180mmHg or <90mmHg at baseline.
• Withdrawal, introduction, or change in dose of hormone replacement therapy (HRT) or the oral contraceptive pill (OCP) and/or certain drugs which are known to interact with ropinirole (e.g. ciprofloxacin, cimetidine, tobacco, omeprazole).

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment	Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of at Least Moderate Depression (MADRS Score: >=18)	Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.	Baseline and Week 12
Average Change of the HAM-D (Hamilton Depression Rating Scale, 17-item-Version) Total Score From Baseline to Final Visit After 12 Weeks of Treatment	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54 (severely ill).	Baseline and Week 12
Average Change of the HAM-D Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of an at Least Moderate Depression (HAM-D Score >= 15) at Baseline	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54(severely ill).	Baseline and Week 12
Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment	Becks Depression Inventory (BDI) is a 21 item self inventory evaluating symptoms of depression, cognition, and physical symptoms of fatigue, weight loss, and lack of interest in sex. The Higher the score represents most severely depressed participants. Score range for each items is 0-3 and Total score 0-63.	Baseline and Week 12
Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of an at Least Mild-moderate Depression (BDI >= 21) at Baseline	Becks Depression Inventory (BDI) is a 21 item self inventory evaluating symptoms of depression, cognition, and physical symptoms of fatigue, weight loss, and lack of interest in sex. The Higher the score represents most severely depressed participants. Score range for each items is 0-3 and total score 0-63.	Baseline and Week 12
Percentage of Participants With at Least Moderate Depression (MADRS Score >= 18) at Baseline and in Week 12	Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.	Baseline and Week 12
Percentage of Participants With at Least Moderate Depression (HAM-D >= 15) at Baseline and in Week 12	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54 (severely ill).	Baseline and Week 12
Percentage of Participants ("Responder") With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline	Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.	Baseline and Week 12
Percentage of Participants ("Responder") With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline in Subjects With Signs of at Least Moderate Depression at Baseline (MADRS Score >= 18)	Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.	Baseline and Week 12
Change in Average MADRS Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria)	Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.	Baseline and Week 12
Change in Average HAM-D Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria)	The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54 (severely ill).	Baseline and Week 12
Change in Average BDI Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria)	Becks Depression Inventory (BDI) is a 21 item self inventory evaluating symptoms of depression, cognition, and physical symptoms of fatigue, weight loss, and lack of interest in sex. The Higher the score represents most severely depressed participants. Score range for each items is 0-3 and Total score 0-63.	Baseline and Week 12
Change in Average International Restless Legs Scale for Severity (IRLS) Scores in All Participants From Baseline to After 1, 4, and 12 Weeks	International Restless Legs Scale for Severity (IRLS)is a series of 10 questions which rate severity from 0-4 points for various questions and total score ranks: Very severe=31-40 points, Severe=21-30 points, Moderate=11-20 points, and Mild=1-10 points, None=0 points	Baseline, Week 1, Week 4, Week 12
Percentage of Participants With a Decrease of International Restless Legs Scale (IRLS) Scores of at Least 6 Points After 1, 4 and 12 Weeks	International Restless Legs Scale for Severity (IRLS)is a series of 10 questions which rate severity from 0-4 points for various questions and total score ranks: Very severe=31-40 points, Severe=21-30 points, Moderate=11-20 points, and Mild=1-10 points, None=0 points	Week 1, Week 4, Week 12
Percentage of Participants With "Much Improved" or "Very Much Improved" on the Clinical Global Impression-Global Improvement Scale After 1, 4 and 12 Weeks	The CGI-I assesses the investigator's impression of the patient's current illness. The time span is the week before the rating and the score range: 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5- minimally worse, 6-much worse, to 7-very much worse.	Week 1, Week 4, Week 12
Change From Average Baseline Score of Subscale of "Somnolence" in the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks	Medical Outcome Study Sleep Scale (MOS-SS)-is a 12 item questionaire assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache. 10 question score from 1-6, 1 question scores 1-5 and 1 question asks average number of hours sleep each night.	Baseline and after Week 12
Change From Average Baseline Scores of Subscale "Sleep Disturbance" of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks	Medical Outcome Study Sleep Scale (MOS-SS)-is a 12 item questionaire assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache. 10 question score from 1-6, 1 question scores 1-5 and 1 question asks average number of hours sleep each night.	Baseline and after Week 12
Change From Average Baseline Scores of Subscale "Sleep Adequacy" of the Medical Outcomes Study Sleep Scale (MOS-SS)to Final Visit After 12 Weeks	Medical Outcome Study Sleep Scale (MOS-SS)-is a 12 item questionaire assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache. 10 question score from 1-6, 1 question scores 1-5 and 1 question asks average number of hours sleep each night.	Baseline and after Week 12
Change From Average Baseline Scores of Subscale "Sleep Quantity" (Hours) of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks		Baseline and after Week 12

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: July 25, 2006
• First Submitted That Met QC Criteria: July 26, 2006
• First Posted (Estimate): July 27, 2006

Study Record Updates

• Last Update Posted (Estimate): June 7, 2012
• Last Update Submitted That Met QC Criteria: May 31, 2012
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: depression; placebo; double-blind; mood; ropinirole; randomised; restless legs syndrome; RLS; germany
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Dyskinesias; Psychomotor Disorders; Parasomnias; Depression; Syndrome; Psychomotor Agitation; Restless Legs Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Ropinirole
• Other Study ID Numbers: RRL106721