Clinical trial NCT02089464: Niche Trial: Navigated Inhibitory rTMS to Contralesional Hemisphere Trial
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke
Lead sponsor: Nexstim Ltd
Sponsor class: INDUSTRY
First posted: 2014-03-17
Enrollment: 199
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: 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.


Eligibility 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.

Primary outcomes:
measure: Upper Extremity Fugl-Meyer Score
timeFrame: Baseline - 6 months post-treatment
Secondary outcomes:
measure: Arm-Research Action Test (ARAT)
timeFrame: Baseline - 6 months post-treatment
measure: Wolf Motor Function Test
timeFrame: Baseline - 6 months post-treatment
measure: NIH Stroke Scale (NIHSS)
timeFrame: Baseline - 6 months post-treatment
measure: Chedoke-McMaster Stroke Assessment (CMSA)
timeFrame: Baseline - 6 months post-treatment
measure: Stroke Impact Scale (SIS)
timeFrame: Baseline - 6 months post-treatment
measure: Patient Health Questionnaire (PHQ9)
timeFrame: Baseline - 6 months post-treatment
measure: Quality of Life Assessment: EuroQol EQ-5D Scale
timeFrame: Baseline - 6 months post-treatment
Other outcomes:
measure: To Assess Safety of Study Device Use, All Serious Adverse Events Will be Recorded and Compared Between Groups
timeFrame: Baseline - 6 months post-treatment
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Downey
country: United States
facility: Rancho Los Amigos National Rehabilitation Center
state: California
city: Atlanta
country: United States
facility: Shepherd Rehabilitation Center
state: Georgia
city: Chicago
country: United States
facility: Rehabilitation Institute of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Indianapolis
state: Indiana
city: Boston
country: United States
facility: Spaulding Rehabilitation Hospital
state: Massachusetts
city: New York
country: United States
facility: Columbia Cornell New York Presbyterian Hospital
state: New York
city: White Plains
country: United States
facility: Burke Medical Research Institute, Weill Cornell Neurology
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: TIRR Memorial Hermann Hospital
state: Texas
Study officials:
affiliation: Shirley Ryan AbilityLab
name: Richard L Harvey, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.