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

Restless Legs Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00357097
• Other study ID #: RRL106721
• Status: Completed
• Phase: Phase 3
• First received: July 25, 2006
• Last updated: May 31, 2012
• Start date: June 2006
• Est. completion date: December 2007

Study information

• Verified date: May 2011
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Moderate to Severe Idiopathic Restless Legs Syndrome (RLS)
• Psychomotor Agitation
• Restless Legs Syndrome
• Syndrome

Intervention

Drug:
• Ropinirole

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Achim	Niedersachsen
Germany	GSK Investigational Site	Anklam	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Bad Homburg	Hessen
Germany	GSK Investigational Site	Bad Saarow	Brandenburg
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bielefeld	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Butzbach	Hessen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Dueren	Nordrhein-Westfalen
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Ellwangen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Freiburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Gelsenkirchen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Gera	Thueringen
Germany	GSK Investigational Site	Goettingen	Niedersachsen
Germany	GSK Investigational Site	Goettingen	Niedersachsen
Germany	GSK Investigational Site	Guetersloh	Nordrhein-Westfalen
Germany	GSK Investigational Site	Halle	Sachsen-Anhalt
Germany	GSK Investigational Site	Hattingen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Herborn	Hessen
Germany	GSK Investigational Site	Hildesheim	Niedersachsen
Germany	GSK Investigational Site	Jena	Thueringen
Germany	GSK Investigational Site	Juelich	Nordrhein-Westfalen
Germany	GSK Investigational Site	Kassel	Hessen
Germany	GSK Investigational Site	Koethen	Sachsen-Anhalt
Germany	GSK Investigational Site	Limburgerhof	Rheinland-Pfalz
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Nuernberg	Bayern
Germany	GSK Investigational Site	Oldenburg	Schleswig-Holstein
Germany	GSK Investigational Site	Ostfildern	Baden-Wuerttemberg
Germany	GSK Investigational Site	Regensburg	Bayern
Germany	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Germany	GSK Investigational Site	Unterhaching	Bayern
Germany	GSK Investigational Site	Wismar	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Wolfsburg	Niedersachsen
Germany	GSK Investigational Site	Wuerzburg	Bayern

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No