Clinical trial NCT00297778: Pramipexole Versus Placebo in Parkinson's Disease (PD) Patients With Depressive Symptoms
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel Group Efficacy Study of Pramipexole and Placebo Administered Orally Over a 12 Week Treatment Phase in Parkinson's Disease Patients With Stable Motor Function and Depressive Symptoms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson Disease
Depression
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-03-01
Enrollment: 296
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Parkinsons Disease (PD) is caused by a decrease of dopamine in a particular part of the brain. Dopamine is a messenger substance (neurotransmitter) that is used by the cells of the brain (nerve cells) to control and harmonize muscle movements. Consequently, the main manifestations of the disease affect movement and include tremor, muscular rigidity, slowness in performing movements and loss of balance.

However, the disease affects also other, non motor functions and may cause other disorders, such as depression. Depression may be a reaction to the disability caused by the disease, but many studies show that depression is more common in PD than in other chronic debilitating illnesses. Moreover, there is also a biological explanation for the phenomenon: dopamine is also used in brain circuits involved in the experience of pleasure, and loss of pleasure in daily physical or social activity is one of the key manifestations of depression.

The objective of the study is to assess whether pramipexole, at doses approved for the treatment of PD symptoms, is more effective than placebo in resolving depressive symptoms in PD patients.

Also data on the safety of the product in the disease will be collected.


Eligibility criteria: Inclusion Criteria:

1. 15-item Geriatric Depression Scale (GDS) \> or = 5
2. Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score on Question #3 \> or = 2
3. Folsteins Mini-Mental State Examination (MMSE) score \> 24
4. Male or female patient with PD (UK PD Brain Bank criteria).
5. Patients diagnosed with idiopathic PD, Stage I-III by the Modified Hoehn and Yahr Scale and optimally controlled PD symptoms .
6. Male or female patients aged 30 - 80 years.
7. Ability to provide written informed consent.
8. Women of childbearing potential must have a negative serum beta-humanchoriongonadotropin (Beta-HCG) pregnancy test at the Screening visit unless surgically sterile or last menstruation \>or = 12 months prior to signing informed consent.
9. Women of childbearing potential must be using an accepted contraceptive.
10. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Previous history of allergic response, lack of efficacy or complications with pramipexole or its excipients.
2. History of suicidal attempts in the last twelve months; presence of suicidal tendencies/potential.
3. Atypical PD syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases.
4. History of PD stereotactic brain surgery.
5. Surgery within 180 days of randomization that would negatively impact the patients participation in the study.
6. History of active epilepsy within the past year.
7. Current psychotherapy or behavior therapy while participating the trial
8. Symptomatic orthostatic hypotension prior to randomization.
9. Malignant melanoma or history of previously treated malignant melanoma.
10. Patients who have received typical neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, selegiline or amphetamine derivatives within the past 3 months.
11. Patients who have received dopamine agonists within the past 30 days
12. Electroconvulsive therapy during the 90 days preceding the screening visit (Visit 1).
13. Patients who are currently lactating.
14. Participation in other investigational drug studies or use of other investigational drugs within the previous 30 days prior to randomization.
15. Any other laboratory assay abnormality, which could interfere with patient participation or interpretation of results, or could increase the risk for the patient
16. Any other clinically significant medical/psychiatric condition, which could interfere with patient participation or interpretation of results, or could increase the risk for the patient

Primary outcomes:
measure: Change From Baseline in the Beck Depression Inventory-Version 1A (BDI-IA) Total Score at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change in BDI-IA Clinical Response (at Least 50% Reduction in Symptoms) at Week 12
timeFrame: Week 12
measure: Change From Baseline in the Geriatric Depression Scale-Short Form (GDS-SF) (15-item Version) Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) Part I Depression Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the UPDRS Part II Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the UPDRS Part III Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the UPDRS Part II+III Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Clinical Global Impressions of Global Improvement (CGI-I) at Week 12
timeFrame: Week 12
measure: Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Overall Index Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the European Quality of Life Scale (EUROQOL (EQ)-5D) Overall Index Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline to End of Maintenance Phase in European Quality of Life Visual Analogue Scale (EUROQOL (EQ) VAS) Pain Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the UPDRS Part I Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in the UPDRS Part IV Total Score at Week 12
timeFrame: Baseline and Week 12
measure: Abnormal Findings: Clinical Laboratory Evaluations (Biochemistry and Haematology)and Vital Signs
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Graz
country: Austria
facility: 248.596.43003 Boehringer Ingelheim Investigational Site
city: Innsbruck
country: Austria
facility: 248.596.43001 Boehringer Ingelheim Investigational Site
city: Linz
country: Austria
facility: 248.596.43005 Boehringer Ingelheim Investigational Site
city: St. Pölten
country: Austria
facility: 248.596.43004 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 248.596.43002 Boehringer Ingelheim Investigational Site
city: Oulu
country: Finland
facility: 248.596.35801 Boehringer Ingelheim Investigational Site
city: Aix en Provence cedex 1
country: France
facility: 248.596.3302B Centre Hospitalier du Pays d'Aix
city: Aix en Provence
country: France
facility: 248.596.3302A Centre Hospitalier du Pays d'Aix
city: Bron cedex
country: France
facility: 248.596.3306A Hôpital Pierre Wertheimer
city: Clermont Ferrand
country: France
facility: 248.596.3308A Hôpital Gabriel Montpied
city: Evreux
country: France
facility: 248.596.3309A Cabinet Médical
city: Lille cedex
country: France
facility: 248.596.3307A Hôpital Roger Salengro
city: Lille cedex
country: France
facility: 248.596.3307B Hôpital Roger Salengro
city: Lille cedex
country: France
facility: 248.596.3307C Hôpital Roger Salengro
city: Marseille cedex 5
country: France
facility: 248.596.3303A Hôpital La Timone
city: Pessac cédex
country: France
facility: 248.596.3305A Hôpital du Haut Levêque
city: Pessac cédex
country: France
facility: 248.596.3305B Hôpital du Haut Levêque
city: Saint Herblain
country: France
facility: 248.596.3301A Hôpital Guillaume et René Laennec
city: Berlin-Steglitz
country: Germany
facility: 248.596.49012 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.596.49002 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.596.49013 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.596.49015 Boehringer Ingelheim Investigational Site
city: Bremerhaven
country: Germany
facility: 248.596.49003 Boehringer Ingelheim Investigational Site
city: Gera
country: Germany
facility: 248.596.49004 Boehringer Ingelheim Investigational Site
city: Karlsruhe
country: Germany
facility: 248.596.49001 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 248.596.49016 Boehringer Ingelheim Investigational Site
city: Marburg
country: Germany
facility: 248.596.49005 Boehringer Ingelheim Investigational Site
city: Mittweida
country: Germany
facility: 248.596.49014 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 248.596.49008 Boehringer Ingelheim Investigational Site
city: Catania
country: Italy
facility: 248.596.39008 Clinica Neurologica I Policlinico di Catania
city: Grosseto
country: Italy
facility: 248.596.39004 Neurologia Ospedale della Misericordia
city: Messina
country: Italy
facility: 248.596.39005 Clinica Neurologica Policlinico G. Martino
city: Milano
country: Italy
facility: 248.596.39009 Istituti Clinici di Perfezionamento
city: Napoli
country: Italy
facility: 248.596.39003 Università degli studi di Napoli "Federico II"
city: Pescara
country: Italy
facility: 248.596.39001 Ospedale Civile S. Spirito, Università "G. D'Annunzio"
city: Roma
country: Italy
facility: 248.596.39007 Clinica Neurologica Policlinico Tor Vergata
city: Torino
country: Italy
facility: 248.596.39006 Neurologia Ospedale Evangelico Valdese
city: 's-Hertogenbosch
country: Netherlands
facility: 248.596.31003 Jeroen Bosch Ziekenhuis, locatie WA
city: Amsterdam
country: Netherlands
facility: 248.596.31007 Afdeling neurologie
city: Blaricum
country: Netherlands
facility: 248.596.31005 Ziekenhuis Gooi-Noord
city: Breda
country: Netherlands
facility: 248.596.31004 Amphia ziekenhuis, Locatie Molengracht
city: Nijmegen
country: Netherlands
facility: 248.596.31002 Canisius-Wilhelmina Ziekenhuis
city: Sittard
country: Netherlands
facility: 248.596.31001 Maasland Ziekenhuis
city: Arendal
country: Norway
facility: 248.596.47002 Boehringer Ingelheim Investigational Site
city: Lillehammer
country: Norway
facility: 248.596.47004 Boehringer Ingelheim Investigational Site
city: Sandvika
country: Norway
facility: 248.596.47003 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 248.596.40003 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 248.596.40004 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 248.596.40005 Boehringer Ingelheim Investigational Site
city: Cluj Napoca
country: Romania
facility: 248.596.40001 Boehringer Ingelheim Investigational Site
city: Iasi
country: Romania
facility: 248.596.40002 Boehringer Ingelheim Investigational Site
city: Targu-Mures
country: Romania
facility: 248.596.40006 Country Clinical Emergency Hospital
city: Moscow
country: Russian Federation
facility: 248.596.70001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 248.596.70003 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 248.596.70002 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 248.596.70004 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 248.596.70005 Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: 248.596.27001 Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: 248.596.27003 Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: 248.596.27007 Boehringer Ingelheim Investigational Site
city: Johannesburg
country: South Africa
facility: 248.596.27008 Boehringer Ingelheim Investigational Site
city: Pretoria
country: South Africa
facility: 248.596.27004 Boehringer Ingelheim Investigational Site
city: Richards Bay
country: South Africa
facility: 248.596.27006 Boehringer Ingelheim Investigational Site
city: Alcorcon (Madrid)
country: Spain
facility: 248.596.34003 Hospital de Alcorcón. Departamento de Neurología
city: Barcelona
country: Spain
facility: 248.596.34001 Hospital Sta Creu i Sant Pau. Departamento de Neurología
city: Barcelona
country: Spain
facility: 248.596.34002 Hospital Clinic i Provincial. Departamento de Neurología
city: Barcelona
country: Spain
facility: 248.596.34005 Hosp. Univ. Vall d'Hebron. Departamento de Neurología
city: Madrid
country: Spain
facility: 248.596.34007 Hosp Gral Univ Gregorio Marañón. Departamento de Neurología
city: San Cugat del Valles (Barcelona)
country: Spain
facility: 248.596.34004 Hospital General de Catalunya. Departamento de Neurología
city: Linköping
country: Sweden
facility: 248.596.46004 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 248.596.46001 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 248.596.46002 Boehringer Ingelheim Investigational Site
city: Donetsk
country: Ukraine
facility: 248.596.38004 Boehringer Ingelheim Investigational Site
city: Kharkiv
country: Ukraine
facility: 248.596.38005 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 248.596.38002 Boehringer Ingelheim Investigational Site
city: Simferopol
country: Ukraine
facility: 248.596.38006 Boehringer Ingelheim Investigational Site
city: Vinnytzya
country: Ukraine
facility: 248.596.38003 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Barone P, Poewe W, Albrecht S, Debieuvre C, Massey D, Rascol O, Tolosa E, Weintraub D. Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2010 Jun;9(6):573-80. doi: 10.1016/S1474-4422(10)70106-X. Epub 2010 May 7.