MedPath

Pramipexole Versus Placebo in Parkinson's Disease (PD) Patients With Depressive Symptoms

Phase 4
Completed
Conditions
Parkinson Disease
Depression
Interventions
Other: Placebo
Registration Number
NCT00297778
Lead Sponsor
Boehringer Ingelheim
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
296
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
pramipexolePramipexoleA daily dose of pramipexole 0.125 mg t.i.d.; titration-to-response up to 1.0 mg t.i.d.
placeboPlaceboPlacebo (matching) tablets
Primary Outcome Measures
NameTimeMethod
Change From Baseline in the Beck Depression Inventory-Version 1A (BDI-IA) Total Score at Week 12Baseline and Week 12

The BDI measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 63 (worst symptoms)

Secondary Outcome Measures
NameTimeMethod
Change in BDI-IA Clinical Response (at Least 50% Reduction in Symptoms) at Week 12Week 12

BDI clinical response was defined as a reduction of ≥50% from baseline

Change From Baseline in the Geriatric Depression Scale-Short Form (GDS-SF) (15-item Version) Total Score at Week 12Baseline and Week 12

The GDS measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 15 (worst symptoms)

Change From Baseline in the UPDRS Part III Total Score at Week 12Baseline and Week 12

The UPDRS part III total score measures the impact of PD on motor skills on an ordinal scale ranging from 0 (normal) to 108 (worst symptoms)

Clinical Global Impressions of Global Improvement (CGI-I) at Week 12Week 12

The CGI-I measures the overall improvement in the participants condition from baseline on an ordinal scale ranging from 1 (very much improved) to 7 (very much worse)

Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Overall Index Score at Week 12Baseline and Week 12

The PDQ-39 measures aspects of health in PD participants, the overall index score is the mean of the eight individual domain scores measured on a continuous scale ranging from 0 (no problem at all) to 100 (maximum level of the problem)

Change From Baseline in the European Quality of Life Scale (EUROQOL (EQ)-5D) Overall Index Score at Week 12Baseline and Week 12

This is a 5-item patient reported measure of health status developed for use in evaluating health and healthcare. It produces a numeric score for health status on which full health has a value of 1 and death has a value of 0. Euro-QOL describes health status in terms of 5 dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The EQ-5D measures health status on a continuous scale ranging from 0 (dead) to 1 (full health)

Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score at Week 12Baseline and Week 12

The SHAPS measures anhedonia (inability to experience pleasure) on an ordinal scale ranging from 0 (no anhedonia) to 14 (worst anhedonia)

Change From Baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) Part I Depression Score at Week 12Baseline and Week 12

The UPDRS part I depression score measures depression on an ordinal scale ranging from 0 (none) to 4 (sustained depression/suicidal thoughts)

Change From Baseline to End of Maintenance Phase in European Quality of Life Visual Analogue Scale (EUROQOL (EQ) VAS) Pain Score at Week 12Baseline and Week 12

The VAS is a method used for the measurement of pain. The patient is asked to place a mark on an uncalibrated (usually 0 - 10 cm) line representing the patient's degree of general pain. The two extremities of the line were taken to represent 'no pain' and 'unbearable pain', respectively. VAS pain scores could range from 0 (no pain) to 100 (unbearable pain).

Change From Baseline in the UPDRS Part I Total Score at Week 12Baseline and Week 12

The UPDRS part I total score measures depression on an ordinal scale ranging from 0 to 16. UPDRS Part I total scores could range from 0 to 16; where higher scores were indicative of worse symptoms.

Change From Baseline in the UPDRS Part IV Total Score at Week 12Baseline and Week 12

The UPDRS Part IV measures motor complications (dyskinesia) and the total score could range from 0 to 23; where higher scores were indicative of worse symptoms.

Abnormal Findings: Clinical Laboratory Evaluations (Biochemistry and Haematology)and Vital SignsBaseline and Week 12
Change From Baseline in the UPDRS Part II Total Score at Week 12Baseline and Week 12

Unified Parkinson's Disease Rating Scale part II total score on FAS The UPDRS part II total score measures the impact of PD on activities of daily living on an ordinal scale ranging from 0 (normal) to 52 (worst symptoms)

Change From Baseline in the UPDRS Part II+III Total Score at Week 12Baseline and Week 12

The UPDRS part II+III total score measures the impact of PD on activities of daily living and motor skills on an ordinal scale ranging from 0 (normal) to 160 (worst symptoms)

Trial Locations

Locations (77)

248.596.43001 Boehringer Ingelheim Investigational Site

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Innsbruck, Austria

248.596.43005 Boehringer Ingelheim Investigational Site

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Linz, Austria

248.596.43003 Boehringer Ingelheim Investigational Site

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Graz, Austria

248.596.43004 Boehringer Ingelheim Investigational Site

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St. Pölten, Austria

248.596.35801 Boehringer Ingelheim Investigational Site

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Oulu, Finland

248.596.40005 Boehringer Ingelheim Investigational Site

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Bucharest, Romania

248.596.70001 Boehringer Ingelheim Investigational Site

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Moscow, Russian Federation

248.596.31001 Maasland Ziekenhuis

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Sittard, Netherlands

248.596.47002 Boehringer Ingelheim Investigational Site

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Arendal, Norway

248.596.40001 Boehringer Ingelheim Investigational Site

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Cluj Napoca, Romania

248.596.40002 Boehringer Ingelheim Investigational Site

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Iasi, Romania

248.596.40006 Country Clinical Emergency Hospital

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Targu-Mures, Romania

248.596.70003 Boehringer Ingelheim Investigational Site

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Moscow, Russian Federation

248.596.70004 Boehringer Ingelheim Investigational Site

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St. Petersburg, Russian Federation

248.596.38003 Boehringer Ingelheim Investigational Site

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Vinnytzya, Ukraine

248.596.38006 Boehringer Ingelheim Investigational Site

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Simferopol, Ukraine

248.596.38004 Boehringer Ingelheim Investigational Site

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Donetsk, Ukraine

248.596.38002 Boehringer Ingelheim Investigational Site

🇺🇦

Kiev, Ukraine

248.596.3303A Hôpital La Timone

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Marseille cedex 5, France

248.596.3308A Hôpital Gabriel Montpied

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Clermont Ferrand, France

248.596.3307C Hôpital Roger Salengro

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Lille cedex, France

248.596.49003 Boehringer Ingelheim Investigational Site

🇩🇪

Bremerhaven, Germany

248.596.3302A Centre Hospitalier du Pays d'Aix

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Aix en Provence, France

248.596.49012 Boehringer Ingelheim Investigational Site

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Berlin-Steglitz, Germany

248.596.49014 Boehringer Ingelheim Investigational Site

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Mittweida, Germany

248.596.49015 Boehringer Ingelheim Investigational Site

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Berlin, Germany

248.596.43002 Boehringer Ingelheim Investigational Site

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Wien, Austria

248.596.31002 Canisius-Wilhelmina Ziekenhuis

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Nijmegen, Netherlands

248.596.3302B Centre Hospitalier du Pays d'Aix

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Aix en Provence cedex 1, France

248.596.3306A Hôpital Pierre Wertheimer

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Bron cedex, France

248.596.49013 Boehringer Ingelheim Investigational Site

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Berlin, Germany

248.596.49005 Boehringer Ingelheim Investigational Site

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Marburg, Germany

248.596.31007 Afdeling neurologie

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Amsterdam, Netherlands

248.596.49002 Boehringer Ingelheim Investigational Site

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Berlin, Germany

248.596.34001 Hospital Sta Creu i Sant Pau. Departamento de Neurología

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Barcelona, Spain

248.596.46004 Boehringer Ingelheim Investigational Site

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Linköping, Sweden

248.596.34003 Hospital de Alcorcón. Departamento de Neurología

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Alcorcon (Madrid), Spain

248.596.3305B Hôpital du Haut Levêque

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Pessac cédex, France

248.596.49001 Boehringer Ingelheim Investigational Site

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Karlsruhe, Germany

248.596.70002 Boehringer Ingelheim Investigational Site

🇷🇺

St. Petersburg, Russian Federation

248.596.38005 Boehringer Ingelheim Investigational Site

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Kharkiv, Ukraine

248.596.34002 Hospital Clinic i Provincial. Departamento de Neurología

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Barcelona, Spain

248.596.49004 Boehringer Ingelheim Investigational Site

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Gera, Germany

248.596.27001 Boehringer Ingelheim Investigational Site

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Cape Town, South Africa

248.596.49008 Boehringer Ingelheim Investigational Site

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München, Germany

248.596.39009 Istituti Clinici di Perfezionamento

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Milano, Italy

248.596.27003 Boehringer Ingelheim Investigational Site

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Cape Town, South Africa

248.596.31005 Ziekenhuis Gooi-Noord

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Blaricum, Netherlands

248.596.47004 Boehringer Ingelheim Investigational Site

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Lillehammer, Norway

248.596.40003 Boehringer Ingelheim Investigational Site

🇷🇴

Bucharest, Romania

248.596.40004 Boehringer Ingelheim Investigational Site

🇷🇴

Bucharest, Romania

248.596.46002 Boehringer Ingelheim Investigational Site

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Stockholm, Sweden

248.596.34007 Hosp Gral Univ Gregorio Marañón. Departamento de Neurología

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Madrid, Spain

248.596.27008 Boehringer Ingelheim Investigational Site

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Johannesburg, South Africa

248.596.27006 Boehringer Ingelheim Investigational Site

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Richards Bay, South Africa

248.596.31003 Jeroen Bosch Ziekenhuis, locatie WA

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's-Hertogenbosch, Netherlands

248.596.31004 Amphia ziekenhuis, Locatie Molengracht

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Breda, Netherlands

248.596.47003 Boehringer Ingelheim Investigational Site

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Sandvika, Norway

248.596.39001 Ospedale Civile S. Spirito, Università "G. D'Annunzio"

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Pescara, Italy

248.596.70005 Boehringer Ingelheim Investigational Site

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St. Petersburg, Russian Federation

248.596.34004 Hospital General de Catalunya. Departamento de Neurología

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San Cugat del Valles (Barcelona), Spain

248.596.34005 Hosp. Univ. Vall d'Hebron. Departamento de Neurología

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Barcelona, Spain

248.596.27007 Boehringer Ingelheim Investigational Site

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Cape Town, South Africa

248.596.27004 Boehringer Ingelheim Investigational Site

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Pretoria, South Africa

248.596.39008 Clinica Neurologica I Policlinico di Catania

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Catania, Italy

248.596.39004 Neurologia Ospedale della Misericordia

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Grosseto, Italy

248.596.39005 Clinica Neurologica Policlinico G. Martino

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Messina, Italy

248.596.39003 Università degli studi di Napoli "Federico II"

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Napoli, Italy

248.596.39006 Neurologia Ospedale Evangelico Valdese

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Torino, Italy

248.596.39007 Clinica Neurologica Policlinico Tor Vergata

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Roma, Italy

248.596.46001 Boehringer Ingelheim Investigational Site

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Stockholm, Sweden

248.596.3309A Cabinet Médical

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Evreux, France

248.596.3307A Hôpital Roger Salengro

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Lille cedex, France

248.596.3307B Hôpital Roger Salengro

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Lille cedex, France

248.596.3305A Hôpital du Haut Levêque

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Pessac cédex, France

248.596.3301A Hôpital Guillaume et René Laennec

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Saint Herblain, France

248.596.49016 Boehringer Ingelheim Investigational Site

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Köln, Germany

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