Evaluate the Effectiveness and Safety of Variable Frequency Stimulation Compared With Constant Frequency Stimulation for Patients With Idiopathic Parkinson's Disease

Evaluate the Effectiveness and Safety of Variable Frequency Stimulation Compared With Constant Frequency Stimulation for Patients With Idiopathic Parkinson's Disease（RESTEP Study）

In the VFS paradigm the stimulation frequency was set to alternate between high and low frequencies, where the frequency of stimulation or frequency combinations can be changed instantaneously according to damage of the moment rhythms. Variable frequency stimulation is a novel dynamic therapy which breaks through the existing single high-frequency stimulation paradigms. It is the world's first VFS therapy for the brain.

Study Overview

• Status: Unknown
• Conditions: Parkinson Disease
• Intervention / Treatment: Procedure: Variable Frequency Stimulation

Detailed Description

In advanced stages of PD, motor symptoms and dyskinesia are effectively treated by deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) . Traditionally, in this procedure, stimulation is set to a constant frequency electrical stimulation with the physician programming the parameters of stimulation frequency, pulse width and amplitude, and stimulated patients' brain nuclei with single frequency, single pulse width and single amplitude of the electric stimulation. Indeed, high frequency stimulation (HFS) of the STN provides consistent, long-term improvement of the cardinal signs of PD . However, the treatment effects of HFS on the axial symptoms of PD, specifically FOG can be poor often causing further impairment. While this can be alleviated by using relatively low frequency stimulation (LFS) , major concerns in the clinical application of LFS exist in regards to its duration of therapeutic benefit. Previous studies have shown that LFS of the STN improves the axial motor signs in some PD patients, but a loss of therapeutic efficacy is seen in the short term. Thereafter, patients may present increased tremor, rigidity and bradykinesia, which is often intolerable outweighing the initial benefits of LFS therapy for FOG. As such, a suitable treatment strategy for FOG remains to be established.

Based on previous findings on the relationships between stimulation frequency and movement rhythm regulation in the human body, The National Engineering Laboratory for Neuromodulation, Tsinghua University, proposes a method of variable frequency stimulation (VFS) for aiding movement.

• Study Type: Interventional
• Enrollment (Anticipated): 106
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Yi Guo, MD; Phone Number: 010-69152530
  • Beijing, China
    • Recruiting
    • General Hospital of PLA
    • Contact: Zhipei Ling, MD; Phone Number: 010-66938339
  • Dalian, China
    • Recruiting
    • The First Affiliated Hospital of Dalian Medical University
    • Contact: Zhanhua Liang; Phone Number: 0411-83635963
  • Nanjing, China
    • Recruiting
    • Nanjing Brain Hospital Affiliated to Nanjing Medical University
    • Contact: Weiguo Liu, MD; Phone Number: 025-82296071
  • Shanghai, China
    • Recruiting
    • Changhai Hospital of Shanghai
    • Contact: Jianmin Liu, MD; Phone Number: 021-31166666
  • Shanghai, China
    • Recruiting
    • Huashan Hospital, Fudan University
    • Contact: Jian Wang, MD; Phone Number: 021-96567576
  • Shenyang, China
    • Recruiting
    • The General Hospital of Shenyang Military
    • Contact: Yingqun Tao; Phone Number: 024-28897782
  • Shenzhen, China
    • Recruiting
    • Second people's Hospital of Shenzhen
    • Contact: Xiaodong Cai, MD; Phone Number: 0755-83216006
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Tiantan Hospital Affiliated to Capital Medical University
      • Contact: Jianguo Zhang, MD; Phone Number: 010-67096767

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients With Idiopathic Parkinson's Disease.
2. ≥18 years,both male and female
3. Patients who under deep brain stimulation
4. MMSE score ≥24
5. H-Y≥2.0 under the medicine off/ constant frequency stimulation state
6. The 14 item of UPDRS-II score ≥1
7. The 15 item of UPDRS-II score ≥2
8. Subjects had an ability to walk ≥ 10 meters independently under the medicine off/ constant frequency stimulation state

Exclusion Criteria:

1. Pregnant women or breastfeeding mothers, or woman who cannot take effective measures to prevent pregnancy.
2. Presence of other diseases affecting walking distance, such as joint disease in lower body, spinal disease, neuropathy, serious heart or lung disease.
3. Diseases seriously affecting health and life, such as tumour, serious liver or kidney diseases etc.
4. Patients with epilepsy etc.
5. Presence of mental disorders or dementia.
6. Patients or their families who cannot comprehend the therapy or patients who are unable to give informed consent voluntarily.
7. Patients whom cannot cooperate well with follow-up requirements.
8. Patients excluded based on the researchers judgement for participation in the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Variable Frequency Stimulation; Subjects in this group received variable frequency stimulation of deep brain stimulation	Procedure: Variable Frequency Stimulation; vary the frequency of the stimulation parameter
Sham Comparator: Constant Frequency Stimulation; Subjects in this group received constant frequency stimulation of deep brain	Procedure: Variable Frequency Stimulation; vary the frequency of the stimulation parameter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stand-Walk-Sit	The total time of patients who complete the Stand-Walk-Sit task	at 3 months compare to baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
United Parkinson's Disease Rate Scale scores	at 3、6 months compare to baseline
The39-item Parkinson's Disease Questionnaire (PDQ-39) scores	at 3、6 months compare to baseline
The Freezing of Gait Questionnaire (FOG-Q) scores	at 3、6 months compare to baseline
Gait and Falls Questionnaire (GFQ) scores	at 3、6 months compare to baseline

Collaborators and Investigators

• Sponsor: Beijing Pins Medical Co., Ltd
• Investigators: Study Chair: Luming Li, Tsinghua University

Publications and helpful links

General Publications

• Jia F, Zhang J, Wang H, Liang Z, Liu W, Wang X, Liu Y, Guo Y, Ling Z, Cai X, Wu X, Wu J, Lv W, Xu X, Zhang W, Li L. Variable- versus constant-frequency deep-brain stimulation in patients with advanced Parkinson's disease: study protocol for a randomized controlled trial. Trials. 2019 Dec 19;20(1):749. doi: 10.1186/s13063-019-3884-4.

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2017
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: January 22, 2017
• First Submitted That Met QC Criteria: February 14, 2017
• First Posted (Actual): February 15, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2018
• Last Update Submitted That Met QC Criteria: March 13, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Variable Frequency Stimulation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: PINS-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No