Deep Brain Stimulation Treatment for Chorea in Huntington's Disease

• Sponsor: Beijing Municipal Administration of Hospitals (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04244513
• Collaborator: Medtronic (Industry)
• Enrollment: 40
• Locations: 3
• Arms: 2
• Anticipated Duration (Months): 46.9
• Patients Per Site: 13.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

1. Evaluating therapeutic effects of globus pallidus internus (GPi) deep brain stimulation (DBS) on Huntington's disease (HD) patients with chorea；

2. Explore the relationship between brain network conditions and DBS efficacy in HD patients

3. Explore the effect of different programmed parameters on the treatment of patients with DBS

Condition or Disease	Intervention/Treatment	Phase
Huntington Disease; Deep Brain Stimulation	Device: Deep brain stimulation	N/A

Detailed Description

1. Evaluating therapeutic effects of GPi-DBS on HD patients with chorea: Clinical data of patients at different treatment time points will be collected, using different clinical assessments. The clinical case report form for HD-DBS is consistent with Enroll HD project and the case report form is attached in the appendix. The main purpose is to determine the efficiency of DBS treatment for HD with chorea by comparing the patients' status before and after surgery.

Primary endpoints: Changes in chorea score of UHDRS, changes in total motor score (UHDRS).

Secondary endpoints: changes in cognition will be assessed by stroop interference test, stroop word reading test, stroop colour naming test, trail making test, symbol digit modality test and mini-mental state examination(MMSE); changes in anxiety assessed by Hamilton Anxiety Scale(HAMA); changes in depression assessed by Hamilton depression scale(HAMD) and Beck Depression Inventory (BDI); changes in the frequency and severity of neuropsychiatric symptoms assessed by the Problem Behaviours Assessment for HD and changes in quality-of-life assessed by UHDRS functional assessment and UHDRS total functional capacity assessment.

2 Explore the relationship between brain network conditions and DBS efficacy in HD patients The electrophysiological signals during the operation of HD patients will be collected and analyzed, and compared with the postoperative disease conditions, to determine the relationship between the patient's EEG activity and the mechanism of disease development, disease progression, and treatment effect.

1. Explore the effect of different programmed parameters on the treatment of patients with DBS After the HD patient is turned on, the patient is programmed to adjust the program control parameters of different patients during adjustment, and the effects of different program control parameters on the patient, tolerance, and related side effects are clarified.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Patients will be randomized into two groups, of which the first group will be routinely activated after surgery and then stimulated for 6 months. The second group of patients will be re-launched 3 months after surgery, continued stimulation for 3 months, and then entered the open study. Patient data will be collected before surgery, 3 months after surgery, and 6 months after surgery.Patients will be randomized into two groups, of which the first group will be routinely activated after surgery and then stimulated for 6 months. The second group of patients will be re-launched 3 months after surgery, continued stimulation for 3 months, and then entered the open study. Patient data will be collected before surgery, 3 months after surgery, and 6 months after surgery.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: This study adopts a blind design. One day before the first programming, the grouper and the programmer will release the cover independently. Only the grouper and the programmer will know the group information of each patient, in which the programmer does not communicate with the patient about the programming parameters. After each programming, the results are uniformly placed in the programmer to keep the others (patients, neurologists) blind about grouping and parameters. The evaluation will be finished by neurologists and video records of the patient's motor assessment. Neurologists do not participate in the surgical treatment and programmer. The statistical team is independent of other researchers. When performing statistical analysis, only the group information is known, the programming parameters corresponding to the group are blinded. The Medtronic company only provides equipment support and does not participate in any clinical research process.
• Primary Purpose: Treatment
• Official Title: Deep Brain Stimulation Treatment for Chorea in Huntington's Disease
• Actual Study Start Date: Feb 1, 2020
• Anticipated Primary Completion Date: Jun 30, 2023
• Anticipated Study Completion Date: Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HD-DBS This group will be routinely activated after surgery and then stimulated for 6 months.	Device: Deep brain stimulation; the HD-DBS arm will be routinely activated after surgery and then stimulated for 6 months(6 months stimulation). The HD-shamDBS arm will be re-launched 3 months after surgery, continued stimulation for 3 months(3 months stimulation), and then entered the open study.
Sham Comparator: HD-sham-DBS This group of patients will be re-launched 3 months after surgery, continued stimulation for 3 months	Device: Deep brain stimulation; the HD-DBS arm will be routinely activated after surgery and then stimulated for 6 months(6 months stimulation). The HD-shamDBS arm will be re-launched 3 months after surgery, continued stimulation for 3 months(3 months stimulation), and then entered the open study.

Outcome Measures

Primary Outcome Measures

1. Unified Huntington's Disease Rating Scale（UHDRS）-total score difference [3 months postoperatively compared between groups]

   Difference between groups in the UHDRS total score at 3 months postoperative；from 0 to 124 points; the higher scores mean a worse outcome

2. Unified Huntington's Disease Rating Scale（UHDRS）-total score difference [6 months postoperatively compared with baseline]

   Difference in the UHDRS total score at 6 months postoperative compared with baseline

Secondary Outcome Measures

1. UHDRS-Chorea subscore difference [6 months postoperatively compared with baseline]

   Difference in the UHDRS chorea subscore at 6 months postoperative compared with baseline

2. Mental Behavior Rating Scale difference [6 months postoperatively compared with baseline]

   the total score of MMSE at 6 months postoperative compared with baseline

3. Mental Behavior Rating Scale difference [6 months postoperatively compared with baseline]

   the total score of BDI at 6 months postoperative compared with baseline

4. EuroQol five dimensions questionnaire (EQ-5D) difference [6 months postoperatively compared with baseline]

   the total score of EQ-5D at 6 months postoperative compared with baseline

5. Neuroimage [preoperative, 3 months and 6 months postoperative]

   MRI

6. electrophysiology [3 to 5 days postoperative]

   EEG and Local field potential (LFP) of GPi and GPe in patients with Huntington's Disease

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Huntington's Disease disgnosis by gene

2. Predominant chorea

3. UHDRS score ≥30

4. Mini-Mental State Examination (MMSE) score meets the education level

5. No plan to change medication within 12 months after randomization

6. Agree to enroll into the clinical trial

Exclusion Criteria:

1. Chorea caused by other diseases

2. Concurrently or previously had other neurological disorders

3. Severe psychiatric disease

4. Unstable condition or severe heart, lung, liver, kidney, or hematopoietic diseases

5. Have a history of cancer unless it has been cured or does not require treatment for the next 5 years

6. Contraindications to an MRI scan

7. Acute psychiatric symptomatology in the last 2 months including suicide ideation, angry or aggressive behaviour, and hallucinations

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Tiantan Hospital	Beijing	Beijing	China	100070
2	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong	China
3	West China Hospital, Sichuan University	Chengdu	Sichuan	China

Sponsors and Collaborators

• Beijing Municipal Administration of Hospitals
• Medtronic

Investigators

• Study Chair: Jianguo Zhang, Ph.D, Beijing Tiantan Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zhang Jianguo, Director of functional neurosurgery in Beijing Tiantan Hospital, Beijing Tiantan Hospital
• ClinicalTrials.gov Identifier: NCT04244513
• Other Study ID Numbers: KY2019-092-03
• First Posted: Jan 28, 2020
• Last Update Posted: Jul 20, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Zhang Jianguo, Director of functional neurosurgery in Beijing Tiantan Hospital, Beijing Tiantan Hospital: Deep brain stimulation; Chorea; Huntington Disease
• Additional relevant MeSH terms: Huntington Disease; Chorea

Study Results

No Results Posted as of Jul 20, 2022