Niche Trial: Navigated Inhibitory rTMS to Contralesional Hemisphere Trial (NICHE)

• ClinicalTrials.gov Identifier: NCT02089464
• Recruitment Status: Completed
• First Posted: March 17, 2014
• Results First Posted: September 1, 2020
• Last Update Posted: September 1, 2020
• Sponsor: Nexstim Ltd
• Information provided by (Responsible Party): Nexstim Ltd

Study Description

Brief Summary:

A pivotal, prospective, multi-center, randomized, controlled, double-blinded study combining active Nexstim NBS-guided 1Hz rTMS or sham-rTMS targeting the healthy hemisphere with standardized task oriented rehabilitation will be conducted in patients with post-stroke motor impairment. The therapy will be provided for 6 weeks and primary outcome assessed 6 months later.

Condition or disease	Intervention/treatment	Phase
Stroke	Device: NBS-guided rTMS; Device: Sham rTMS; Procedure: Task oriented rehabilitation	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 199 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pivotal Phase III, Prospective, Multicenter, Double Blinded, Randomized, Sham Controlled Trial to Determine the Therapeutic Effects of Navigation Guided 1 Hz rTMS Administered to the Contralesional Hemisphere as Adjuvant to Task Oriented Rehabilitation in Patients With Ischemic or Hemorrhagic Stroke
• Study Start Date: April 2014
• Actual Primary Completion Date: May 2016
• Actual Study Completion Date: May 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: NBS-rTMS + task-oriented rehabilitation; NBS-guided rTMS + task-oriented rehabilitation	Device: NBS-guided rTMS; Other Name: Nexstim; Procedure: Task oriented rehabilitation
Sham Comparator: Sham rTMS + task-oriented rehabilitation; Sham rTMS + task-oriented rehabilitation	Device: Sham rTMS; Procedure: Task oriented rehabilitation

Outcome Measures

Primary Outcome Measures :

1. Upper Extremity Fugl-Meyer Score [ Time Frame: Baseline - 6 months post-treatment ]
   Number of Participants with Improvement in Upper Extremity Fugl-Meyer (UEFM) Score at 6 Months Post-treatment equal or exceeding the Minimal Clinically Important Difference (MCID) of 5 points (MCID).

Secondary Outcome Measures :

1. Arm-Research Action Test (ARAT) [ Time Frame: Baseline - 6 months post-treatment ]
   Scale minimum 0, maximum 57. Greater values indicate better motor function.
2. Wolf Motor Function Test [ Time Frame: Baseline - 6 months post-treatment ]
   Time in seconds to perform test tasks. Shorter time indicates better motor function.
3. NIH Stroke Scale (NIHSS) [ Time Frame: Baseline - 6 months post-treatment ]
   Scale is a measure of neurological functioning, with higher scores reflecting greater deficit (minimum 0,maximum 42)
4. Chedoke-McMaster Stroke Assessment (CMSA) [ Time Frame: Baseline - 6 months post-treatment ]
   Scale minimum 1, maximum 7. Higher values indicate better motor function of hand.
5. Stroke Impact Scale (SIS) [ Time Frame: Baseline - 6 months post-treatment ]
   Score used to detect the consequences of stroke on physical functioning and activities of daily living. The SIS-16 is a 16 item survey that inquires about daily tasks performed over the previous 2 weeks. Scale minimum 16, maximum 80. Higher values indicate better function
6. Patient Health Questionnaire (PHQ9) [ Time Frame: Baseline - 6 months post-treatment ]
   The possible presence and severity of depression will be assessed using the Patient Health Questionnaire (PHQ9). PHQ9 is a scale with a minimum value 0 and maximum of 27. Higher values indicate more depressed mood
7. Quality of Life Assessment: EuroQol EQ-5D Scale [ Time Frame: Baseline - 6 months post-treatment ]
   The EuroQoL EQ-5D is a visual analog scale scale from 0 (minimum) to 100 (maximum) assessing quality of life. Higher values indicate better quality of life.

Other Outcome Measures:

1. To Assess Safety of Study Device Use, All Serious Adverse Events Will be Recorded and Compared Between Groups [ Time Frame: Baseline - 6 months post-treatment ]
   Serious Adverse Events were recorded and their occurrence was compared between treatment arms

Eligibility Criteria

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

Criteria

Inclusion Criteria :

• ≥ 18 years of age
• An ischemic or hemorrhagic stroke suffered 3-12 months prior to the study;
• no other known brain abnormalities by history;
• A one-sided stroke resulting in upper extremity paresis
• A Chedoke-McMaster Stroke Assessment arm stage and hand stage of 3-6 for the affected limb

Exclusion Criteria

• Implanted metallic parts of implanted electronic devices, including pacemakers, defibrillators, or implant medication pump;
• Pregnant or trying to become pregnant; Lack of pregnancy established in females of child-bearing potential by a negative urine pregnancy test at screening.
• Active alcohol abuse, illicit drug use or drug abuse or significant mental illness
• Patients suffering from depression as measured by a score of >10 on the Patient Health Questionnaire (PHQ9). For clarity, patients diagnosed with depression which is controlled with stable anti-depressive medication and in whom PHQ9 is <10 are eligible to participate in the trial.
• History of epilepsy, defined as at least two unprovoked seizures occurring greater than 24 hours apart or diagnosis of an epilepsy syndrome, OR a seizure within the last 12 months.
• Any condition that would prevent the subject from giving voluntary informed consent;
• An implanted brain stimulator;
• Any metal in head with the exception of dental work or any ferromagnetic metal elsewhere in the body;
• Enrolled or plans to enroll in an interventional trial during this study;
• Scalp wounds or infections;
• Claustrophobia precluding MRI;
• A fixed contraction deformity in the affected limb that would prevent normal dexterity if patient were neurologically intact;
• Excessive spasticity as indicated by the Modified Ashworth Spasticity (MAS) Scale >2/4 in either elbow flexors, wrist flexors or finger flexors of the affected limb;i
• previous stroke with residual deficits (TIAs not a reason for exclusion);
• premorbid (retrospective) modified Rankin Scale (mRS) score ≥2 of any aetiology;
• a concurrent progressive neurologic disorder, acute coronary syndrome, severe heart disease (NYHA Classification > 3), or other major medical condition,
• confirmed or suspected lower-limb fracture preventing mobilization,
• patients requiring palliative care
• patients planning to undergo any other occupational therapy during the 6 week active treatment period of the trial (see section 5.2 for study schedule) than what is provided in the study
• A recent injection of botulinium toxin to the affected upper limb in the last 3 months, or the need of an injection of botulinum toxin anytime during the study period and follow up.
• A recent injection of phenol to the affected upper limb in the last 6 months, or the need of an injection of phenol anytime during the study period and follow up.
• Ataxia as measured by a score > 1 on item 7 (limb ataxia) of the NIH stroke scale.
• Severe sensory deficits as measured by a score of 2 on item 8 of the NIH stroke scale.
• Severe aphasia as measured by a score of > 2 on item 9 (best language) of the NIH stroke scale.
• Severe neglect as measured by a score of 2 on item 11 (extinction and inattention) of the NIH stroke scale.
• Patients unable to comprehend or follow verbal commands
• Based on PI's or local physician's assessment patient unable to tolerate the trial procedure due to medical condition
• A Mini mental status exam (MMSE) <25.

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic

Phoenix, Arizona, United States, 85054

United States, California

Rancho Los Amigos National Rehabilitation Center

Downey, California, United States, 90242

United States, Georgia

Shepherd Rehabilitation Center

Atlanta, Georgia, United States, 30309

United States, Illinois

Rehabilitation Institute of Chicago

Chicago, Illinois, United States, 60611

United States, Indiana

Indiana University Indianapolis

Indianapolis, Indiana, United States, 46202

United States, Massachusetts

Spaulding Rehabilitation Hospital

Boston, Massachusetts, United States, 02129

United States, New York

Columbia Cornell New York Presbyterian Hospital

New York, New York, United States, 10032

Burke Medical Research Institute, Weill Cornell Neurology

White Plains, New York, United States, 10605

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27705

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45267

Ohio State University

Columbus, Ohio, United States, 43210

United States, Texas

TIRR Memorial Hermann Hospital

Houston, Texas, United States, 77030

Sponsors and Collaborators

Nexstim Ltd

Investigators

• Principal Investigator: Richard L Harvey, MD; Shirley Ryan AbilityLab

More Information

Publications of Results:

Harvey RL, Edwards D, Dunning K, Fregni F, Stein J, Laine J, Rogers LM, Vox F, Durand-Sanchez A, Bockbrader M, Goldstein LB, Francisco GE, Kinney CL, Liu CY; NICHE Trial Investigators *. Randomized Sham-Controlled Trial of Navigated Repetitive Transcranial Magnetic Stimulation for Motor Recovery in Stroke. Stroke. 2018 Sep;49(9):2138-2146. doi: 10.1161/STROKEAHA.117.020607.

• Responsible Party: Nexstim Ltd
• ClinicalTrials.gov Identifier: NCT02089464
• Other Study ID Numbers: NX92325
• First Posted: March 17, 2014
• Results First Posted: September 1, 2020
• Last Update Posted: September 1, 2020
• Last Verified: August 2020

Additional relevant MeSH terms:

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases