Controlled Trial With Deep Brain Stimulation in Patients With Early Parkinson's Disease

Study Overview
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Brief Summary
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Earlystim Study: Patients are randomized either to medical treatment or subthalamic stimulation. The observation period was 2 years. The primary outcome criterium: PDQ-39. Post study Follow up studies: After the 24 months observation period also BMT patients could be operated and all patients will be observed for 10 years or longer to elucidate whether earlier stimulation has advantages (or drawbacks) compared to later stimulation.

Detailed Description
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Parkinsons' disease is one of the most disabling chronic neurological diseases. It can be treated sufficiently until motor complications with fluctuations of mobility and dyskinesias develop. The quality of life and the social and occupational functioning is relentlessly deteriorating with longer disease duration once the complications of conservative therapy develop. High-frequency stimulation of the subthalamic nucleus especially improves the motor complications of Parkinson's disease and preliminary data suggest that also the quality of life and psychosocial handicap are improved. So far this therapy is only used for patients which have already undergone personal, professional and social degradation due to motor complications of the disease. The aim of this study is to assess the use of this therapy in earlier stages of the disease, when motor complications have just developed and before patients are significantly affected in their social and occupational functioning. The main study (Earlystim) was finished in March 2012 and published in February 2013 (Schuepbach WM, Rau J, Knudsen K, et al. Neurostimulation for Parkinson's disease with early motor complications. N Engl J Med. Feb 14 2013;368(7):610-622.) Patients, who were treated with BMT only in the Earlystim Study were privileged to be operated after the 24 months and a follow up phase of 5 years was planned to elucidate whether earlier stimulation has advantages (or drawbacks) compared to later stimulation. As operated patients fare better in terms of quality of life and other outcomes (see publication), it will be important to know if patients who are operated earlier keep an advantage in all thoses parameters over those who were operated later or if those operated later will catch up after surgery. Also the pattern of adverse events among earlier and later operated patients may differ. These issues can be addressed with the post-study follow-up (PSFU) studies of the patients of the Earlystim trial. The results of these investigations elucidate longterm issues of DBS in PD and may affect the recommendations of surgery for patients.

Official Title
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The Effect of Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) on Quality of Life in Comparison to Best Medical Treatment in Patients With Complicated Parkinson's Disease and Preserved Psychosocial Competence (EARLYSTIM-study)

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Kinetra and Soletra (neurostimulator, Medtronic)
* Drug: Best Medical Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Idiopathic Parkinson's Disease Hoehn and Yahr stage ≤ 2.5 in the best onmed condition Disease duration > 4 years Presence of fluctuations and/or dyskinesias for no more than 3 years One of the two following forms of impairment: Impairment in activities of daily living (UPDRS II > 6) due to PD-symptoms despite medical treatment in the worst condition or Impairment of social and occupational functioning (measured with a modified SOFAS) due to PD-symptoms despite medical treatment (51-80%) PDQ-39 completed Written informed consent For the patients in France a social security number is required Exclusion Criteria Major depression with suicidal thoughts (Beck Depression Inventory > 25) Dementia (Mattis Score ≤ 130) Acute psychosis Need for nursing care Any medical or psychological problems which may interfere with a smooth conduction of the study protocol (e.g. cancer with a limited life expectancy) Drug or alcohol addiction Surgical contraindications Fertile women not using adequate contraceptive methods Women who are pregnant or breast feeding Illiteracy or insufficient language skills (German or French) to complete the questionnaires Simultaneous participation in another clinical trial except that other trial does not affect the Earlystim study as approved and documented by the steering committee

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DBS treatment<br>Patients in this arm are treated with Deep Brain Stimulation (DBS) of the Nucleus subthalamicus with the device Kinetra and Soletra (neurostimulator, Medtronic) and addtionally get best medical treatment | Device: Kinetra and Soletra (neurostimulator, Medtronic)<br>* Patients in this arm were implanted with a neurostimulator (Kinetra and Soletra from Medtronic) are stimulated. Additionally the get best medical treatment.<br>|
| Active Comparator: BMT treatment<br>Patients in this arm get best medical treatment only. | Drug: Best Medical Treatment<br>* Patients in this arm get best medical treatment only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PDQ-39 | Difference in the PDQ-39 summary index at 24 months compared to the baseline assessment. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UPDRS part III | Change in the Unified Parkinson's disease Rating Scale (UPDRS) part III | 24 months | 
| UPDRS II scale | Change in the UPDRS II scale | 24 months | 
| Safety | Frequency, type and severity of therapy related adverse events of medication or DBS, Change in medication (L-DOPA equivalents) | 24 months | 
| UPDRS VI scale | Change in the UPDRS VI scale | 24 months | 
| SCOPA-PS | Change in the SCOPA-PS scale | 24 months | 
| BDI scale | Change in the BDI scale | 24 months | 
| MADRS scale | Change in the MADRS scale | 24 months | 
| BPRS scale | Change in the BPRS scale | 24 months | 
| Mattis Dementia Scale | Change in the Mattis Dementia Scale | 24 months | 
| Ardouin Behaviour Scale | Change in the Ardouin Behaviour Scale | 24 months | 
| Starkstein-Apathy Scale | Change in the Starkstein-Apathy Scale | 24 months | 
| professional Fitness scale | Change in the professional Fitness scale | 24 months | 
| SF-36 scale | Change in the SF-36 scale | 24 months | 
| pain (VAS) scale, | Change in the pain (VAS) scale | 24 months | 
| clinical global impression (CGI-GI) scale | change in the clinical global impression (CGI-GI) scale | 24 months | 
| best-state | Change in the number of hours per day in the best-state | 24 months | 
| best state dyskinesias | Frequency and severity of best state dyskinesias | 24 months | 
| Sleeping-hours per day | Sleeping-hours per day | 24 months | 
| Gait | Changes in gait | 24 months | 
| Speech | Changes in speech | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson Disease, Deep Brain Stimulation, PDQ-39