Clinical trial NCT00354133: Controlled Trial With Deep Brain Stimulation in Patients With Early Parkinson's Disease
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Parkinson Disease
Keywords: Parkinson Disease
Deep Brain Stimulation
PDQ-39
Lead sponsor: German Parkinson Study Group (GPS)
Sponsor class: OTHER
Collaborators: name: University Hospital Schleswig-Holstein
name: Assistance Publique - Hôpitaux de Paris
name: KKS Netzwerk
First posted: 2006-07-20
Enrollment: 251
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: PDQ-39
timeFrame: 24 months
Secondary outcomes:
measure: UPDRS part III
timeFrame: 24 months
measure: UPDRS II scale
timeFrame: 24 months
measure: Safety
timeFrame: 24 months
measure: UPDRS VI scale
timeFrame: 24 months
measure: SCOPA-PS
timeFrame: 24 months
measure: BDI scale
timeFrame: 24 months
measure: MADRS scale
timeFrame: 24 months
measure: BPRS scale
timeFrame: 24 months
measure: Mattis Dementia Scale
timeFrame: 24 months
measure: Ardouin Behaviour Scale
timeFrame: 24 months
measure: Starkstein-Apathy Scale
timeFrame: 24 months
measure: professional Fitness scale
timeFrame: 24 months
measure: SF-36 scale
timeFrame: 24 months
measure: pain (VAS) scale,
timeFrame: 24 months
measure: clinical global impression (CGI-GI) scale
timeFrame: 24 months
measure: "best"-state
timeFrame: 24 months
measure: "best" state dyskinesias
timeFrame: 24 months
measure: Sleeping-hours per day
timeFrame: 24 months
measure: Gait
timeFrame: 24 months
measure: Speech
timeFrame: 24 months
Other outcomes:
Locations:
city: Grenoble Cedex
country: France
facility: Michallon Hospital, CHU Grenoble, Service de Neurologie, BP217
city: Lyon
country: France
facility: Service de Neurologie C, Hôpital Neurologique et neurochirurgical Pierre Wertheimer , 59 Bd Pinel 69677 BRON Cedex
city: Marseille
country: France
facility: Centre hospitalier La Timone, Service de neurologie et pathologie du mouvement,Boulevard Jean Moulin
city: Nantes
country: France
facility: "Hôpital Nord Laënnec Boulevard Jacques-Monod - Saint-Herblain
city: Paris Cedex 13
country: France
facility: CIC, CHU Pitié-Salpêtrière, 47-83 Bd de l'Hôpital
city: Poitiers
country: France
facility: Hôpital La Milétrie, Tour Jean Bernard, 350 Av Jacques Cœur, BP 577
city: Rouen
country: France
facility: Centre Hospitalo-Universitaire de Rouen, Charles Nicolle, bat. DV, 1 rue de Germont
city: Toulouse
country: France
facility: Centre d'investigation Clinique, Pavillon Riser, Hôpital Purpan,Place du Dr Baylac TSA 40031
city: Berlin
country: Germany
facility: Klinik und Poliklinik für Neurologie, Charite
city: Duesseldorf
country: Germany
facility: Neurologische Klinik der Universität, Moorenstr. 5
city: Freiburg
country: Germany
facility: Neurologische Universitätsklinik Freiburg, Breisacher Str. 64
city: Kassel
country: Germany
facility: Paracelsus-Elena-Klinik, Kassel, Klinikstrasse 16
city: Kiel
country: Germany
facility: Klinik für Neurologie, Universitätsklinikum Schleswig-Holstein, Schittenhelmstr. 10
city: Köln
country: Germany
facility: Klinik und Poliklinik für Neurologie
city: München
country: Germany
facility: Klinikum der Universität München Neurologische Klinik und Poliklinik - Großhadern, Marchioninistr. 15
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Klinik für Neurochirurgie, Hoppe-Seyler-Str.3
Study officials:
affiliation: Department of Neurology, Christian-Albrechts-University Kiel, Schittenhelmstr. 10, D 24105 Kiel
name: Guenther Deuschl, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Groupe Hospitalier Pitié- Salpêtrière, Fédération des Maladies du Système Nerveux, 47-83 Boulevard de l´Hôpital, F- 75651 Paris Cedex 13
name: Marie Vidailhet, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. No abstract available.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.