TY - JOUR
T1 - Subthalamic deep brain stimulation with a constant-current device in Parkinson's disease
T2 - An open-label randomised controlled trial
AU - Okun, Michael S.
AU - Gallo, Bruno V.
AU - Mandybur, George
AU - Jagid, Jonathan
AU - Foote, Kelly D.
AU - Revilla, Fredy J.
AU - Alterman, Ron
AU - Jankovic, Joseph
AU - Simpson, Richard
AU - Junn, Fred
AU - Verhagen, Leo
AU - Arle, Jeff E.
AU - Ford, Blair
AU - Goodman, Robert R.
AU - Stewart, R. Malcolm
AU - Horn, Stacy
AU - Baltuch, Gordon H.
AU - Kopell, Brian H.
AU - Marshall, Frederick
AU - Peichel, De Lea
AU - Pahwa, Rajesh
AU - Lyons, Kelly E.
AU - Tröster, Alexander I.
AU - Vitek, Jerrold L.
AU - Tagliati, Michele
N1 - Funding Information:
BVG, RP, KEL, MT, AIT, and JLV are paid consultants for St Jude Medical Neuromodulation Division. MSO is a consultant for the National Parkinson Foundation; has received grants from National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS), National Parkinson Foundation, Parkinson Alliance; has received no industry-related honoraria for more than 24 months; and has publication Royalties in Demos, Cambridge, Manson, Human. BVG is a consultant for Cyberonics Inc, Medtronic Inc, Novartis Pharmaceuticals, St Jude Medical Neuromodulation Division, and TEVA pharmaceuticals; has received grants from Medtronic Inc, Pfizer Pharma, GlaxoSmithKline, and St Jude Medical Neuromodulation Division. GM, JJag, KDF, and RA have received honoraria from Medtronic Inc. FJR is a consultant for Lundbeck. JJan is a consultant for Allergan, Chelsea Therapeutics, EMD Serono, Lundbeck Inc, Merz Pharmaceuticals, and Teva Pharmaceutical Industries Ltd; has received grants from Allergan, Allon Therapeutics, Ceregene Inc, Chelsea Therapeutics, Diana Helis Henry Medical Research Foundation, EMD Serono, Huntington's Disease Society of America, Huntington Study Group, Impax Pharmaceuticals, Ipsen Limited, Lundbeck Inc, Michael J Fox Foundation for Parkinson Research, Medtronic, Merz Pharmaceuticals, NIH, National Parkinson Foundation, Neurogen, St Jude Medical Neuromodulation Division, Teva Pharmaceutical Industries Ltd, University of Rochester, and Parkinson Study Group; and has royalties in Elsevier, Lippincott Williams and Wilkins, and UpToDate. LV is a consultant for Impax Pharma, Boston Scientific, and Medtronic Inc. JA has received honoraria from Medtronic; is a consultant for Allen Medical, Boston Scientific, Globus Medical, and St Jude Medical Neuromodulation Division (not related to DBS); and is a shareholder and scientific adviser at SpineBridge. BF is in the advisory board for Medtronic Inc. RG is a consultant for Medtronic Inc and NeuroPace. RMS is a consultant for St Jude Medical Neuromodulation Division for internal training purposes. BK is a consultant for Medtronic Inc and Neurostream/Victholm Bionics. FM received travel support from St Jude Medical Neuromodulation Division to attend the investigator start-up meeting for this trial; is a site-investigator for a St Jude Medical Neuromodulation Division-sponsored study in essential tremor; is a member of the Data and Safety Monitoring Board for trials sponsored by the Veterans Administration, and by Toyama Pharmaceuticals; and receives grant support as a site investigator for studies sponsored by the NINDS, the Fox Foundation, TEVA pharmaceuticals, Medivation Inc, CHDI, the Batten Disease Support and Research Association, and the FDA. He has received unrestricted educational grant support in the past from Medtronic Inc. DP is an employee of St Jude Medical Neuromodulation Division. RP is a consultant for St Jude Medical Neuromodulation Division (study design and blind reviewer), Teva Neuroscience, GlaxoSmithKline, GE Healthcare, EMD Serono, Boehinger Ingelheim, Medtronic Inc, Impax Pharma, Novartis, Adamas Pharma, and Biogen. KL is a consultant for Acorda, Medtronic Inc, St Jude Medical Neuromodulation Division (study design and DSMB), and Teva Neuroscience. AT has received grants and honoraria from Medtronic Inc; is a consultant for Medtronic Inc, Boston Scientific, and St Jude Medical Neuromodulation Division (Neuropsychological Testing recommendations and Data Safety Monitoring Board). JLV is a consultant for Boston Scientific, Medtronic Inc, and St Jude Medical Neuromodulation Division (DSMB) and a member of the DSMB for Ceregene. MT has received honoraria from Medtronic Inc and is a consultant for St Jude Medical Neuromodulation Division for internal training purposes. RS, FJ, SH, GHB, declare that they have no conflicts of interest.
PY - 2012/2
Y1 - 2012/2
N2 - Background: The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus. Methods: This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18-80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474. Findings: Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87-4·16]; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups. Interpretation: Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation. Funding: St Jude Medical Neuromodulation Division.
AB - Background: The effects of constant-current deep brain stimulation (DBS) have not been studied in controlled trials in patients with Parkinson's disease. We aimed to assess the safety and efficacy of bilateral constant-current DBS of the subthalamic nucleus. Methods: This prospective, randomised, multicentre controlled trial was done between Sept 26, 2005, and Aug 13, 2010, at 15 clinical sites specialising in movement disorders in the USA. Patients were eligible if they were aged 18-80 years, had Parkinson's disease for 5 years or more, and had either 6 h or more daily off time reported in a patient diary of moderate to severe dyskinesia during waking hours. The patients received bilateral implantation in the subthalamic nucleus of a constant-current DBS device. After implantation, computer-generated randomisation was done with a block size of four, and patients were randomly assigned to the stimulation or control group (stimulation:control ratio 3:1). The control group received implantation without activation for 3 months. No blinding occurred during this study, and both patients and investigators were aware of the treatment group. The primary outcome variable was the change in on time without bothersome dyskinesia (ie, good quality on time) at 3 months as recorded in patients' diaries. Patients were followed up for 1 year. This trial is registered with ClinicalTrials.gov, number NCT00552474. Findings: Of 168 patients assessed for eligibility, 136 had implantation of the constant-current device and were randomly assigned to receive immediate (101 patients) or delayed (35 patients) stimulation. Both study groups reported a mean increase of good quality on time after 3 months, and the increase was greater in the stimulation group (4·27 h vs 1·77 h, difference 2·51 [95% CI 0·87-4·16]; p=0·003). Unified Parkinson's disease rating scale motor scores in the off-medication, on-stimulation condition improved by 39% from baseline (24·8 vs 40·8). Some serious adverse events occurred after DBS implantation, including infections in five (4%) of 136 patients and intracranial haemorrhage in four (3%) patients. Stimulation of the subthalamic nucleus was associated with dysarthria, fatigue, paraesthesias, and oedema, whereas gait problems, disequilibrium, dyskinesia, and falls were reported in both groups. Interpretation: Constant-current DBS of the subthalamic nucleus produced significant improvements in good quality on time when compared with a control group without stimulation. Future trials should compare the effects of constant-current DBS with those of voltage-controlled stimulation. Funding: St Jude Medical Neuromodulation Division.
UR - http://www.scopus.com/inward/record.url?scp=84855987459&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(11)70308-8
DO - 10.1016/S1474-4422(11)70308-8
M3 - Article
C2 - 22239915
AN - SCOPUS:84855987459
SN - 1474-4422
VL - 11
SP - 140
EP - 149
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 2
ER -