Clinical trial NCT03053726: Evaluate the Effectiveness and Safety of Variable Frequency Stimulation Compared With Constant Frequency Stimulation for Patients With Idiopathic Parkinson's Disease
Official title: Evaluate the Effectiveness and Safety of Variable Frequency Stimulation Compared With Constant Frequency Stimulation for Patients With Idiopathic Parkinson's Disease（RESTEP Study）
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Parkinson Disease
Keywords: Variable Frequency Stimulation
Lead sponsor: Beijing Pins Medical Co., Ltd
Sponsor class: INDUSTRY
First posted: 2017-02-15
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Stand-Walk-Sit
timeFrame: at 3 months compare to baseline
Secondary outcomes:
measure: United Parkinson's Disease Rate Scale scores
timeFrame: at 3、6 months compare to baseline
measure: The39-item Parkinson's Disease Questionnaire (PDQ-39) scores
timeFrame: at 3、6 months compare to baseline
measure: The Freezing of Gait Questionnaire (FOG-Q) scores
timeFrame: at 3、6 months compare to baseline
measure: Gait and Falls Questionnaire (GFQ) scores
timeFrame: at 3、6 months compare to baseline
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital Affiliated to Capital Medical University
state: Beijing
city: Beijing
country: China
facility: General Hospital of PLA
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
city: Nanjing
country: China
facility: Nanjing Brain Hospital Affiliated to Nanjing Medical University
city: Shanghai
country: China
facility: Changhai Hospital of Shanghai
city: Shanghai
country: China
facility: Huashan hospital, Fudan university
city: Shenyang
country: China
facility: The General Hospital of Shenyang Military
city: Shenzhen
country: China
facility: Second People's Hospital of Shenzhen
Study officials:
affiliation: Tsinghua University
name: Luming Li
role: STUDY_CHAIR
References:
citation: 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.