## Protocol Section
### Identification Module
**NCT ID:** NCT06415682

**Brief Title:** The Efficacy and Mechanism of SMA+M1 Repetitive Transcranial Magnetic Stimulation on Freezing of Gait in PD

**Official Title:** The Efficacy and Mechanism of SMA+M1 Repetitive Transcranial Magnetic Stimulation on Freezing of Gait in PD

#### Organization Study ID Info
**ID:** 2024-SR-290
#### Organization
**Class:** OTHER
**Full Name:** The First Affiliated Hospital with Nanjing Medical University
### Status Module
#### Completion Date
**Date:** 2024-12-06

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-23

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-12-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-05
**Study First Submit QC Date:** 2024-05-10
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** The First Affiliated Hospital with Nanjing Medical University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This study is a double-blinded randomized study examining the efficacy of the double-site (M1+SMA) repetitive transcranial magnetic stimulation on Freezing of Gait (FOG) in patients with Parkinson's disease. The investigators hypothesize that treatment using magnetic stimulation on double site (including M1-LL and SMA) will improve FOG and gait symptoms in patients with Parkinson's disease.

**Detailed Description:** Patients in the double-site group underwent ten sessions of double-site high frequency rTMS over the bilateral primary motor cortex of the lower leg and supplementary motor area, whereas patients in the single-site group underwent ten sessions of single-site active magnetic stimulation with high frequency rTMS over the bilateral primary motor cortex of the lower leg. In addition, patients in the sham group underwent 10 sessions of sham rTMS on bilateral primary motor cortex of the lower leg. Assessments of FOG severity, gait, motor symptoms, excitability of cortex motor (using transcranial magnetic stimulation), plasma indicators and multimodal magnetic resonance were performed three times: at baseline, one day post intervention, one month post intervention.

### Conditions Module

**Conditions:**

- Parkinson Disease

**Keywords:**

- Parkinson's disease

- gait symptoms

- freezing of gait

- TMS

- neural mechanism

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** DOUBLE

**Who Masked:**

- PARTICIPANT

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 53

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients in the Experimental group underwent ten sessions of double-site high frequency rTMS over the bilateral M1 of the lower leg and SMA.

**Intervention Names:**

- Device: SMA+M1 Transcranial Magnetic Stimulation

**Label:** double-site high frequency rTMS over the bilateral M1 of the lower leg and SMA

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Patients in the Active Comparator group underwent ten sessions of single-site active magnetic stimulation with high frequency rTMS over the bilateral M1 of the lower leg.

**Intervention Names:**

- Device: M1 Transcranial Magnetic Stimulation

**Label:** single-site high frequency rTMS over the bilateral M1 of the lower leg

**Type:** ACTIVE_COMPARATOR

#### Arm Group 3

**Description:** Patients in the Sham Comparator group underwent ten sessions of double sham rTMS on the bilateral M1 of the lower leg.

**Intervention Names:**

- Device: Sham Transcranial Magnetic Stimulation

**Label:** sham magnetic stimulation on the bilateral M1 of the lower leg

**Type:** SHAM_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- double-site high frequency rTMS over the bilateral M1 of the lower leg and SMA

**Description:** The M1 stimulation session consisted 40 trains of 10-Hz rTMS with the protocol of 5s train session and 25s intertrain intervals. There were 4000 pulses per day for M1-LL (unilateral stimulation 2000 pulses). For SMA stimulation, a 5s burst of 10Hz rTMS was repeated 20 times (1000 pulse, 20 minutes' duration).

Patients in the Experimental group underwent ten sessions of double-site high frequency rTMS over the bilateral primary motor cortex (M1) of the lower leg and supplementary motor area (SMA).

**Name:** SMA+M1 Transcranial Magnetic Stimulation

**Type:** DEVICE

#### Intervention 2

**Arm Group Labels:**

- single-site high frequency rTMS over the bilateral M1 of the lower leg

**Description:** The M1 stimulation session consisted 40 trains of 10-Hz rTMS with the protocol of 5s train session and 25s intertrain intervals. There were 4000 pulses per day for M1-LL (unilateral stimulation 2000 pulses). Patients in the Active Comparator group underwent ten sessions of single-site active magnetic stimulation with high frequency rTMS over the bilateral M1 of the lower leg.

**Name:** M1 Transcranial Magnetic Stimulation

**Type:** DEVICE

#### Intervention 3

**Arm Group Labels:**

- sham magnetic stimulation on the bilateral M1 of the lower leg

**Description:** Patients in the Sham Comparator group underwent 10 sessions of double sham rTMS on M1 of the lower leg.

**Name:** Sham Transcranial Magnetic Stimulation

**Type:** DEVICE

### Outcomes Module

#### Primary Outcomes

**Description:** The Freezing of Gait questionnaire will be used to quantify the frequency and severity of FOG. The score will be compared to the baseline. The minimum and maximum values of the FOGQ are 0 and 24. A higher score means a worse outcome. The differences in FOGQ scores before and after treatment can be used to evaluate the effect of TMS treatment.

**Measure:** Changes of Freezing of Gait severity

**Time Frame:** Assessed at baseline, one day post intervention, one month post intervention

#### Secondary Outcomes

**Description:** The New Freezing of Gait questionnaire will be used to quantify the frequency and severity of FOG. The score will be compared to the baseline. The minimum and maximum values of the NFOGQ are 0 and 28. A higher score means a worse outcome. The differences in NFOGQ scores before and after treatment can be used to evaluate the effect of TMS treatment.

**Measure:** Freezing of Gait severity assessment

**Time Frame:** Assessed at baseline, one day post intervention, one month post intervention

**Description:** The measure mainly reflects the overall severity of Parkinson's disease motor symptoms and non-motor symptoms. The minimum value is 0 and the maximum value is 132. A higher score means a worse outcome. The score will be compared to the baseline. The differences in MDS-UPDRS III part scores before and after treatment can be used to evaluate the effect of TMS treatment.

**Measure:** Changes of Movement Disorder Society Unified Parkinson's disease rating scale part III (MDS-UPDRS-III)

**Time Frame:** Assessed at baseline, one day post intervention, one month post intervention

**Description:** Gait speed (m/s) was evaluated at baseline, one day post intervention, one month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. The differences in gait speed before and after treatment can be used to evaluate the effect of TMS treatment.

**Measure:** Changes of Gait speed

**Time Frame:** Assessed at baseline, one day post intervention, one month post intervention

**Description:** Stride length (cm) was evaluated at baseline, one day post intervention, one month post intervention using a portable Inertial Measurement Unit system during a 5-m timed Up-and-Go (TUG) test. The differences in stride length before and after treatment can be used to evaluate the effect of TMS treatment.

**Measure:** Changes of Stride length

**Time Frame:** Assessed at baseline, one day post intervention, one month post intervention

**Description:** Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF) are conducted by TMS devices to assess the cortical excitation and inhibition. SICI was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with 2ms, 3ms, 4ms interstimulus interval between conditioning and test stimuli. ICF was assessed with a subthreshold conditioning stimulus (80% RMT) and a supra-threshold test stimulus (1 mV MEP) with 10, 12, 15 ms interstimulus interval between conditioning and test stimuli. For SICF, a subthreshold first stimulus (S1) intensity was set at 1 mV and a subsequent suprathreshold second stimulus (S2) intensity was set at RMT. Interstimulus intervals were 1.0 to 5.0 milliseconds with increments of 0.5 millisecond.The differences in SICI, ICF and SICF before and after treatment can be used to evaluate the effect of TMS treatment.

**Measure:** Changes in Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short-interval intracortical facilitation (SICF)

**Time Frame:** Assessed at baseline, one day post intervention

**Description:** The functional connectivity in the brain cortex will be recorded by functional MRI. The differences in brain regions' functional connectivity before and after treatment can be used to evaluate the effect of TMS treatment.

**Measure:** Changes in functional connectivity in the brain cortex

**Time Frame:** Assessed at baseline, one day post intervention

**Description:** Studying the brain structure among groups. The differences in brain microstructure before and after treatment can be used to evaluate the effect of TMS treatment.

**Measure:** Changes in brain structure

**Time Frame:** Assessed at baseline, one day post intervention

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. aged between 40-80 years;
2. diagnosis of idiopathic Parkinson's disease (PD) according to the Movement Disorder Society clinical diagnostic criteria;
3. patients were stable on dopaminergic treatment for at least 3 months;
4. Item 3 of the Freezing of Gait Questionnaire(FOG-Q) scored ≥1;
5. Patients experienced FOG during an interview.

Exclusion Criteria:

1. comorbidities of major neurologic diseases other than PD;
2. suffer from musculoskeletal disorders that could have interfered with their ability to walk;
3. presence of contraindications for transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI);
4. marked tremor interfered with TMS detection;
5. previously receiving any kinds of TMS interventions;
6. severe cognitive impairment making cooperation impossible \[Mini Mental State Examination (MMSE) \< 24\];
7. were unable to walk independently during the OFF state.

**Healthy Volunteers:** True

**Maximum Age:** 80 Years

**Minimum Age:** 40 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** kezhong_zhang1969@126.com

**Name:** Kezhong Zhang

**Phone:** 13770840575

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** The First Affiliated Hospital with Nanjing Medical University

**Name:** Kezhong Zhang

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020734

- Term: Parkinsonian Disorders

- ID: D000001480

- Term: Basal Ganglia Diseases

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000009069

- Term: Movement Disorders

- ID: D000080874

- Term: Synucleinopathies

- ID: D000019636

- Term: Neurodegenerative Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

### Condition Browse Module - Browse Leaves

- ID: M13213

- Name: Parkinson Disease

- Relevance: HIGH

- As Found: Parkinson's Disease

- ID: M22494

- Name: Parkinsonian Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M25603

- Name: Ganglion Cysts

- Relevance: LOW

- As Found: Unknown

- ID: M16358

- Name: Synovial Cyst

- Relevance: LOW

- As Found: Unknown

- ID: M4774

- Name: Basal Ganglia Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12029

- Name: Movement Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M2217

- Name: Synucleinopathies

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000010300

- Term: Parkinson Disease

### Misc Info Module

- Version Holder: 2024-05-31
