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

NCT ID: NCT00354133

Last Updated: 2018-06-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 251 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2022-03-31

Brief 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.

Detailed 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.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DBS treatment

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

Group Type: ACTIVE_COMPARATOR

Kinetra and Soletra (neurostimulator, Medtronic)

Intervention Type: DEVICE

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

BMT treatment

Patients in this arm get best medical treatment only.

Group Type: ACTIVE_COMPARATOR

Best Medical Treatment

Intervention Type: DRUG

Patients in this arm get best medical treatment only

Interventions

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.

Intervention Type: DEVICE

Best Medical Treatment

Patients in this arm get best medical treatment only

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Schleswig-Holstein

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: collaborator

KKS Netzwerk

NETWORK

Sponsor Role: collaborator

German Parkinson Study Group (GPS)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guenther Deuschl, Prof.

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Christian-Albrechts-University Kiel, Schittenhelmstr. 10, D 24105 Kiel

Marie Vidailhet, Prof.

Role: PRINCIPAL_INVESTIGATOR

Groupe Hospitalier Pitié- Salpêtrière, Fédération des Maladies du Système Nerveux, 47-83 Boulevard de l´Hôpital, F- 75651 Paris Cedex 13

Locations

Michallon Hospital, CHU Grenoble, Service de Neurologie, BP217

Grenoble, , 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, , 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, , France

Klinik und Poliklinik für Neurologie, Charite

Berlin, , Germany

Klinik und Poliklinik für Neurologie

Cologne, , Germany

Neurologische Klinik der Universität, Moorenstr. 5

Düsseldorf, , Germany

Neurologische Universitätsklinik Freiburg, Breisacher Str. 64

Freiburg im Breisgau, , Germany

Paracelsus-Elena-Klinik, Kassel, Klinikstrasse 16

Kassel, , Germany

Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Schittenhelmstr. 10

Kiel, , Germany

Klinikum der Universität München Neurologische Klinik und Poliklinik - Großhadern, Marchioninistr. 15

München, , Germany

Universitätsklinikum Tübingen, Klinik für Neurochirurgie, Hoppe-Seyler-Str.3

Tübingen, , Germany

Countries

France; Germany

References

Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, Halbig 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, Brefel Courbon C, Vesper J, Schnitzler A, Wojtecki L, Houeto JL, Bataille B, Maltete D, Damier P, Raoul S, Sixel-Doering F, Hellwig D, Gharabaghi A, Kruger R, Pinsker MO, Amtage F, Regis JM, Witjas T, Thobois S, Mertens P, Kloss M, Hartmann A, Oertel WH, Post B, Speelman H, Agid Y, Schade-Brittinger C, Deuschl G; EARLYSTIM Study Group. Neurostimulation for Parkinson's disease with early motor complications. N Engl J Med. 2013 Feb 14;368(7):610-22. doi: 10.1056/NEJMoa1205158.

Reference Type: RESULT

PMID: 23406026 (View on PubMed)

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. No abstract available.

Reference Type: RESULT

PMID: 23697520 (View on PubMed)

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. 2016 Aug;31(8):1183-91. doi: 10.1002/mds.26740.

Reference Type: RESULT

PMID: 27506638 (View on PubMed)

Lhommee E, Wojtecki L, Czernecki V, Witt K, Maier F, Tonder L, Timmermann L, Halbig TD, Pineau F, Durif F, Witjas T, Pinsker M, Mehdorn M, Sixel-Doring F, Kupsch A, Kruger R, Elben S, Chabardes S, Thobois S, Brefel-Courbon C, Ory-Magne F, Regis JM, Maltete D, Sauvaget A, Rau J, Schnitzler A, Schupbach M, Schade-Brittinger C, Deuschl G, Houeto JL, Krack P; EARLYSTIM study group. Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial. Lancet Neurol. 2018 Mar;17(3):223-231. doi: 10.1016/S1474-4422(18)30035-8.

Reference Type: RESULT

PMID: 29452685 (View on PubMed)

Schupbach 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.

Reference Type: RESULT

PMID: 25399678 (View on PubMed)

Deuschl G, Schupbach 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. 2013 Jan;19(1):56-61. doi: 10.1016/j.parkreldis.2012.07.004. Epub 2012 Jul 28.

Reference Type: RESULT

PMID: 22841616 (View on PubMed)

Pinto S, Nebel A, Rau J, Espesser R, Maillochon P, Niebuhr O, Krack P, Witjas T, Ghio A, Cuartero MC, Timmermann L, Schnitzler A, Hesekamp H, Meier N, Mullner J, Halbig TD, Moller B, Paschen S, Paschen L, Volkmann J, Barbe MT, Fink GR, Becker J, Reker P, Kuhn AA, Schneider GH, Fraix V, Seigneuret E, Kistner A, Rascol O, Brefel-Courbon C, Ory-Magne F, Hartmann CJ, Wojtecki L, Fradet A, Maltete D, Damier P, Le Dily S, Sixel-Doring F, Benecke P, Weiss D, Wachter T, Pinsker MO, Regis J, Thobois S, Polo G, Houeto JL, Hartmann A, Knudsen K, Vidailhet M, Schupbach M, Deuschl G; EARLYSTIM Study Group. Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease. Mov Disord. 2023 Feb;38(2):212-222. doi: 10.1002/mds.29282. Epub 2022 Dec 3.

Reference Type: DERIVED

PMID: 36461899 (View on PubMed)

Schuepbach WMM, Tonder L, Schnitzler A, Krack P, Rau J, Hartmann A, Halbig TD, Pineau F, Falk A, Paschen L, Paschen S, Volkmann J, Dafsari HS, Barbe MT, Fink GR, Kuhn A, Kupsch A, Schneider GH, Seigneuret E, Fraix V, Kistner A, Chaynes PP, Ory-Magne F, Brefel-Courbon C, Vesper J, Wojtecki L, Derrey S, Maltete D, Damier P, Derkinderen P, Sixel-Doring F, Trenkwalder C, Gharabaghi A, Wachter T, Weiss D, Pinsker MO, Regis JM, Witjas T, Thobois S, Mertens P, Knudsen K, Schade-Brittinger C, Houeto JL, Agid Y, Vidailhet M, Timmermann L, Deuschl G; EARLYSTIM study group. Quality of life predicts outcome of deep brain stimulation in early Parkinson disease. Neurology. 2019 Mar 5;92(10):e1109-e1120. doi: 10.1212/WNL.0000000000007037. Epub 2019 Feb 8.

Reference Type: DERIVED

PMID: 30737338 (View on PubMed)

Related Links

http://www.kompetenznetz-parkinson.de/

(German Research Collaboration, funded by the German Ministry of Research)

http://www.kks.uni-marburg.de/

(Homepage Coordination Center for Clinical Studies to STN Study, Language: German)

http://www.kks.uni-marburg.de/

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.

Other Identifiers

A 121/06

Identifier Type: -

Identifier Source: org_study_id