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

Parkinson Disease Clinical Trial

— EARLYSTIM  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00354133
• Other study ID #: A 121/06
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: July 2006
• Est. completion date: March 2022

Study information

• Verified date: June 2018
• Source: German Parkinson Study Group (GPS)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 251
• Est. completion date: March 2022
• Est. primary completion date: March 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Idiopathic Parkinson's Disease

• Hoehn and Yahr stage = 2.5 in the best "on"med 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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Device:
• Kinetra and Soletra (neurostimulator, Medtronic)
Patients in this arm were implanted with a neurostimulator (Kinetra and Soletra from Medtronic) are stimulated. Additionally the get best medical treatment.

Drug:
• Best Medical Treatment
Patients in this arm get best medical treatment only

Locations

Country	Name	City	State
France	Michallon Hospital, CHU Grenoble, Service de Neurologie, BP217	Grenoble Cedex
France	Service de Neurologie C, Hôpital Neurologique et neurochirurgical Pierre Wertheimer , 59 Bd Pinel 69677 BRON Cedex	Lyon
France	Centre hospitalier La Timone, Service de neurologie et pathologie du mouvement,Boulevard Jean Moulin	Marseille
France	"Hôpital Nord Laënnec Boulevard Jacques-Monod - Saint-Herblain	Nantes
France	CIC, CHU Pitié-Salpêtrière, 47-83 Bd de l'Hôpital	Paris Cedex 13
France	Hôpital La Milétrie, Tour Jean Bernard, 350 Av Jacques Cœur, BP 577	Poitiers
France	Centre Hospitalo-Universitaire de Rouen, Charles Nicolle, bat. DV, 1 rue de Germont	Rouen
France	Centre d'investigation Clinique, Pavillon Riser, Hôpital Purpan,Place du Dr Baylac TSA 40031	Toulouse
Germany	Klinik und Poliklinik für Neurologie, Charite	Berlin
Germany	Neurologische Klinik der Universität, Moorenstr. 5	Duesseldorf
Germany	Neurologische Universitätsklinik Freiburg, Breisacher Str. 64	Freiburg
Germany	Paracelsus-Elena-Klinik, Kassel, Klinikstrasse 16	Kassel
Germany	Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Schittenhelmstr. 10	Kiel
Germany	Klinik und Poliklinik für Neurologie	Köln
Germany	Klinikum der Universität München Neurologische Klinik und Poliklinik - Großhadern, Marchioninistr. 15	München
Germany	Universitätsklinikum Tübingen, Klinik für Neurochirurgie, Hoppe-Seyler-Str.3	Tübingen

Sponsors (4)

Lead Sponsor	Collaborator
German Parkinson Study Group (GPS)	Assistance Publique - Hôpitaux de Paris, KKS Netzwerk, University of Schleswig-Holstein

Countries where clinical trial is conducted

France,  Germany, 

References & Publications (6)

Dams J, Balzer-Geldsetzer M, Siebert U, Deuschl G, Schuepbach WM, Krack P, Timmermann L, Schnitzler A, Reese JP, Dodel R; EARLYSTIM-investigators. Cost-effectiveness of neurostimulation in Parkinson's disease with early motor complications. Mov Disord. 20 — View Citation

Deuschl G, Schade-Brittinger C, Agid Y; EARLYSTIM Study Group. Neurostimulation for Parkinson's disease with early motor complications. N Engl J Med. 2013 May 23;368(21):2038. doi: 10.1056/NEJMc1303485. — View Citation

Deuschl G, Schüpbach M, Knudsen K, Pinsker MO, Cornu P, Rau J, Agid Y, Schade-Brittinger C. Stimulation of the subthalamic nucleus at an earlier disease stage of Parkinson's disease: concept and standards of the EARLYSTIM-study. Parkinsonism Relat Disord. — View Citation

Lhommée E, Wojtecki L, Czernecki V, Witt K, Maier F, Tonder L, Timmermann L, Hälbig TD, Pineau F, Durif F, Witjas T, Pinsker M, Mehdorn M, Sixel-Döring F, Kupsch A, Krüger R, Elben S, Chabardès S, Thobois S, Brefel-Courbon C, Ory-Magne F, Regis JM, Maltêt — View Citation

Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Hälbig TD, Hesekamp H, Navarro SM, Meier N, Falk D, Mehdorn M, Paschen S, Maarouf M, Barbe MT, Fink GR, Kupsch A, Gruber D, Schneider GH, Seigneuret E, Kistner A, Chaynes P, Ory-Magne F, — View Citation

Schüpbach WM, Rau J, Houeto JL, Krack P, Schnitzler A, Schade-Brittinger C, Timmermann L, Deuschl G. Myths and facts about the EARLYSTIM study. Mov Disord. 2014 Dec;29(14):1742-50. doi: 10.1002/mds.26080. Epub 2014 Nov 14. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PDQ-39	Difference in the PDQ-39 summary index at 24 months compared to the baseline assessment.	24 months
Secondary	UPDRS part III	Change in the Unified Parkinson's disease Rating Scale (UPDRS) part III	24 months
Secondary	UPDRS II scale	Change in the UPDRS II scale	24 months
Secondary	Safety	Frequency, type and severity of therapy related adverse events of medication or DBS, Change in medication (L-DOPA equivalents)	24 months
Secondary	UPDRS VI scale	Change in the UPDRS VI scale	24 months
Secondary	SCOPA-PS	Change in the SCOPA-PS scale	24 months
Secondary	BDI scale	Change in the BDI scale	24 months
Secondary	MADRS scale	Change in the MADRS scale	24 months
Secondary	BPRS scale	Change in the BPRS scale	24 months
Secondary	Mattis Dementia Scale	Change in the Mattis Dementia Scale	24 months
Secondary	Ardouin Behaviour Scale	Change in the Ardouin Behaviour Scale	24 months
Secondary	Starkstein-Apathy Scale	Change in the Starkstein-Apathy Scale	24 months
Secondary	professional Fitness scale	Change in the professional Fitness scale	24 months
Secondary	SF-36 scale	Change in the SF-36 scale	24 months
Secondary	pain (VAS) scale,	Change in the pain (VAS) scale	24 months
Secondary	clinical global impression (CGI-GI) scale	change in the clinical global impression (CGI-GI) scale	24 months
Secondary	"best"-state	Change in the number of hours per day in the "best"-state	24 months
Secondary	"best" state dyskinesias	Frequency and severity of "best" state dyskinesias	24 months
Secondary	Sleeping-hours per day	Sleeping-hours per day	24 months
Secondary	Gait	Changes in gait	24 months
Secondary	Speech	Changes in speech	24 months

External Links

•   (German Research Collaboration, funded by the German Ministry of Research)
•   (Homepage Coordination Center for Clinical Studies to STN Study, Language: German)
•   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.