Deep Brain Stimulation (DBS) for Early Stage Parkinson's Disease (PD)

• ClinicalTrials.gov Identifier: NCT00282152
• Recruitment Status: Completed
• First Posted: January 25, 2006
• Results First Posted: May 30, 2017
• Last Update Posted: May 30, 2017
• Sponsor: Vanderbilt University Medical Center
• Information provided by (Responsible Party): David Charles, Vanderbilt University Medical Center

Study Description

Brief Summary:

Bilateral subthalamic nucleus deep brain stimulation (B-STN DBS) is one of the most effective surgical treatments for PD patients suffering from levodopa-induced motor complications. The relatively low incidence of permanent adverse effects and the potential for neuroprotection and alteration of the natural course of PD suggest a highly favorable benefit-to-risk ratio of this procedure. Since neuroprotection is best applied early in the disease course when there are more surviving neurons, we believe that further investigation of this procedure is warranted. The proposed pilot study will provide the necessary data to substantiate the safety and tolerability of the procedure as well as provide data for the design of a full-scale, multicenter trial to investigate the hypothesis that B-STN DBS is a safe and effective treatment to slow the progression of PD.

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Device: B-STN DBS; Drug: Optimal drug therapy	Not Applicable

Detailed Description:

This pilot trial is designed specifically to collect the preliminary safety and tolerability data necessary to conduct a future phase III clinical trial to investigate the hypothesis that deep brain stimulation of the subthalamic nucleus in subjects with early Parkinson's will slow the progression of the disease.

The study design is a prospective, randomized, blinded, single-center trial comparing the safety and tolerability of B-STN DBS + Optimal Drug Therapy (ODT) vs. (ODT) alone (control, standard of care) in 30 subjects (15 per group) with early PD (Hoehn and Yahr stage II when off medication).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Safety and Tolerability of Neurostimulation in Early Stage Parkinson's Disease
• Study Start Date: March 2006
• Actual Primary Completion Date: January 2012
• Actual Study Completion Date: October 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: ODT; Optimal drug therapy: The drugs used on this study are not investigational. They are drugs for Parkinson's disease that are standard of care. The drug form, dosage, frequency and duration will vary.	Drug: Optimal drug therapy; The drugs used on this study are not investigational. They are drugs for Parkinson's disease that are standard of care. The drug form, dosage, frequency and duration will vary. Examples of drugs used include carbidopa/levodopa, pramipexole, ropinirole, and selegiline.
Experimental: DBS+ODT; Subjects receive bilateral subthalamic nucleus (B-STN) DBS and continue to take optimal drug therapy as prescribed by their treating neurologist. B-STN DBS: Deep brain stimulation (DBS) of both the right and left sub-thalamic nucleus (STN) is an FDA approved treatment for mid- and advanced PD. DBS is not approved for early stage PD. In mid- and advanced stage Parkinson's disease, using DBS in this area of the brain lessens symptoms and allows patients to take less drug to control the disease. Dosage and frequency are not applicable to the DBS. Once the DBS is placed, unless deemed necessary, it will not be removed. Optimal drug therapy: The drugs used on this study are not investigational. They are drugs for Parkinson's disease that are standard of care. The drug form, dosage, frequency and duration will vary.	Device: B-STN DBS; Deep brain stimulation (DBS) of both the right and left sub-thalamic nucleus (STN) is an FDA approved treatment for advanced PD. In mid- and advanced stage Parkinson's disease, using DBS in this area of the brain lessens symptoms and allows patients to take less drug to control the disease. Dosage and frequency are not applicable to the DBS. Once the DBS is placed, unless deemed necessary, it will not be removed.; Drug: Optimal drug therapy; The drugs used on this study are not investigational. They are drugs for Parkinson's disease that are standard of care. The drug form, dosage, frequency and duration will vary. Examples of drugs used include carbidopa/levodopa, pramipexole, ropinirole, and selegiline.

Outcome Measures

Primary Outcome Measures :

1. Safety: Time to Reach a 4 Point Increase (Worsening) in Unified Parkinson's Disease Rating Scale (UPDRS) Motor Score [ Time Frame: baseline to 24 months ]
   The primary hypothesis of this feasibility trial was focused on safety and tolerability and that the DBS+ODT group would not worsen more quickly than the ODT group.
2. Levodopa Equivalents, Change From Baseline [ Time Frame: baseline to 24 months ]
   100 mg of levodopa with a dopa-decarboxylase inhibitor = 133 mg of controlled-release levodopa preparations = total levodopa dose + (total levodopa dose x 0.33) of levodopa with dopa-decarboxylase and entacapone = 1 mg of pergolide, pramipexole, or lisuride = 5 mg of ropinirole = 3.3 mg of rotigotine

Secondary Outcome Measures :

1. Change in UPDRS Part I, Mentation Behavior and Mood [ Time Frame: baseline to 24 months ]
   Score: 0-16 0 =normal, 16 = most disability
2. Change in UPDRS Part II, Activities of Daily Living [ Time Frame: baseline to 24 months ]
   Score: 0-52 0 =normal, 52 = most limited
3. Change in UPDRS Part III, Motor Examination, Excluding Rigidity [ Time Frame: baseline to 24 months ]
   Score: 0-56 0 = full movement, 56 = most limited
4. Change in UPDRS Part IV, Complications of Therapy [ Time Frame: baseline to 24 months ]
   Score: 0-23 0 =no complications, 23 = most complications
5. Change in Total UPDRS [ Time Frame: baseline to 24 months ]

   The Total Unified Parkinson's Disease Rating Scale (UPDRS) is a composite scale, consisting of four sections that evaluate mood and behavior, activities of daily living, motor symptoms, and complications of medical therapy.

   Range is 0 to 16, with 16 being maximal disability

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients must have a clinical diagnosis of probable idiopathic PD.
• Demonstrated response to dopaminergic therapy, defined as demonstrating at least 30% improvement in parkinsonian motor signs, based upon the UPDRS motor examination subscore, following the administration of their dopamine agonist (DA) drug(s) during the screening neurological examination.
• Hoehn and Yahr (H&Y) stage II when OFF medication.
• No contraindications to surgery.
• Age between 50 and 75 years old.
• Available for follow-up for four years.
• Informed Consent: The subject understands the risks, benefits, and alternatives to the study procedures and participation in the study.
• MRI within normal range for age.
• Levodopa or dopamine agonist therapy for greater than six months but less than or equal to four years.

Exclusion Criteria:

• Evidence of an alternative diagnosis or secondary parkinsonism, as suggested by features unusual early in the clinical course: Prominent postural instability, freezing phenomena, or hallucinations unrelated to medications in the first 3 years after symptom onset; dementia preceding motor symptoms; supranuclear gaze palsy (other than restriction of upward gaze) or slowing of vertical saccades in the first year; severe, symptomatic dysautonomia unrelated to medications; documentation of a condition known to produce parkinsonism and plausibly connected to the subject's symptoms (such as suitably located focal brain lesions or neuroleptic use within the past 6 months)
• Uncontrolled medical condition or clinically significant medical disease that would increase the risk of developing pre- or postoperative complications (e.g., significant cardiac or pulmonary disease, uncontrolled hypertension).
• Evidence of dementia
• Major psychiatric disorder
• Previous brain operation or injury.
• Active participation in another clinical trial for the treatment of PD.
• Patients who have demand cardiac pacemakers or implantable cardioverter defibrillators (ICD's).
• Patients who have medical conditions that require repeat MRI scans or diathermy treatments.
• Evidence of existing dyskinesias or motor fluctuations.

Contacts and Locations

Sponsors and Collaborators

Vanderbilt University Medical Center

Investigators

• Principal Investigator: P. David Charles, MD; Vanderbilt University Department of Neurology

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Millan SH, Hacker ML, Turchan M, Molinari AL, Currie AD, Charles D. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index. Parkinsons Dis. 2017;2017:7163801. doi: 10.1155/2017/7163801. Epub 2017 Jun 6.

Charles PD, Dolhun RM, Gill CE, Davis TL, Bliton MJ, Tramontana MG, Salomon RM, Wang L, Hedera P, Phibbs FT, Neimat JS, Konrad PE. Deep brain stimulation in early Parkinson's disease: enrollment experience from a pilot trial. Parkinsonism Relat Disord. 2012 Mar;18(3):268-73. doi: 10.1016/j.parkreldis.2011.11.001. Epub 2011 Nov 21.

• Responsible Party: David Charles, Associate Professor of Neurology, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT00282152 History of Changes
• Other Study ID Numbers: 040797; 1363 ( Other Identifier: Clinical Research Center ); G050016 ( Other Identifier: FDA IDE )
• First Posted: January 25, 2006
• Results First Posted: May 30, 2017
• Last Update Posted: May 30, 2017
• Last Verified: March 2017

Keywords provided by David Charles, Vanderbilt University Medical Center:

Early Stage Parkinson's Disease; Parkinson's Disease; Deep Brain Stimulation; PD; DBS

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases