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

Boehringer Ingelheim296 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

296

Conditions

Parkinson Disease Depression

Eligibility

Sex: ALLMin age: 30 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change From Baseline in the Beck Depression Inventory-Version 1A (BDI-IA) Total Score at Week 12

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

Time frame: Baseline and Week 12

Secondary Outcomes

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

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

Time frame: Week 12

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

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

Time frame: Baseline and Week 12

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

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

Time frame: Baseline and Week 12

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

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

Time frame: Baseline and Week 12

Change From Baseline in the UPDRS Part II Total Score at 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)

Time frame: Baseline and Week 12

Change From Baseline in the UPDRS Part III Total Score at 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)

Time frame: Baseline and Week 12

Change From Baseline in the UPDRS Part II+III Total Score at 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)

Time frame: Baseline and Week 12

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

Time frame: Week 12

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

Time frame: Baseline and Week 12

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

Time frame: Baseline and Week 12

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

Time frame: Baseline and Week 12

Change From Baseline in the UPDRS Part I Total Score at 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.

Time frame: Baseline and Week 12

Change From Baseline in the UPDRS Part IV Total Score at 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.

Time frame: Baseline and Week 12

Abnormal Findings: Clinical Laboratory Evaluations (Biochemistry and Haematology)and Vital Signs

Time frame: Baseline and Week 12

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

Overview

Conditions

Interventions

Eligibility

Locations (77)

Outcomes

Primary Outcomes

Secondary Outcomes