Clinical trial NCT06303869: Deep Brain Stimulation Motor Ventral Thalamus (VOP/VIM) for Restoration of Speech and Upper-limb Function in People With Subcortical Stroke
Official title: Deep Brain Stimulation Motor Ventral Thalamus (VOP/VIM) for Restoration of Speech and Upper-limb Function in People With Subcortical Stroke
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stroke
Brain Disease
Central Nervous System Diseases
Nervous System Diseases
Cardiovascular Diseases
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2024-03-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, non-randomized, open-label, descriptive, experimental.
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this study is to verify whether the use of deep brain stimulation can improve motor function of the hand and arm and speech abilities for people following a stroke. Participants will undergo a surgical procedure to implant deep brain stimulation electrode leads. The electrodes will be connected to external stimulators and a series of experiments will be performed to identify the types of movements that the hand and arm can make and how speech abilities are affected by the stimulation. The implant will be removed after less than 30 days. Results of this study will provide the foundation for future studies evaluating the efficacy of a minimally-invasive neuro-technology that can be used in clinical neuro-rehabilitation programs to restore speech and upper limb motor functions in people with subcortical strokes, thereby increasing independence and quality of life.

Detailed description: The study is designed to assess the assistive effects of DBS (i.e., immediate effects when the stimulation is turned ON) and obtain preliminary evidence for therapeutic effects (i.e., long-lasting effects with stimulation OFF). Researchers will 1) quantify the ability to recruit face muscles with electrical stimulation of the motor thalamus in patients with subcortical stroke, 2) quantify the ability to recruit arm and hand muscles with electrical stimulation of the motor thalamus in patients with subcortical stroke, and 3) verify if the delivery of DBS has effects on the central nervous system with clinical measures.

Eligibility criteria: Inclusion Criteria:

1. Participants must have suffered a single, ischemic, or hemorrhagic stroke more than 6 months before the time of enrollment with dysarthria as a result.
2. Participants must be between the ages of 18 and 75 years old. (Participants outside this age range may be at an increased medical risk and have an increased risk of fatigue during testing).
3. English speaker.
4. Participant must score ≤ 80% in at least 4 categories of the perceptual speech assessment (speech intelligibility, listener effort, speech naturalness, articulatory precision, speech rate, overall voice quality, and/or overall speech severity). OR ≤ 80% in at least 3 categories of the perceptual speech assessment AND ≤ 27 on the Communicative Participation Item Bank.

Exclusion Criteria:

1. Patients who refuse participation in the study.
2. Patients with gross anatomical variances in MR imaging or cerebral vascular accidents involving thalamic and cerebellar areas.
3. Patients with no clinical condition to undergo DBS implantation or highly dependent on anticoagulation therapy.
4. Patients who cannot undergo pre-operative MRIs or could not complete the pre-operative assessments.
5. Participants must not have any serious disease or disorder (ex. neurological condition other than stroke, cancer, severe cardiac or respiratory disease, renal failure, etc.) or cognitive impairments that could affect their ability to participate in this study.
6. Female participants of child-bearing age must not be pregnant, planning to become pregnant for the next 9 months, or breast feeding.
7. Participants must not be receiving anticoagulants.
8. Severe claustrophobia.
9. Participants must not be on anti-spasticity or anti-epileptic medications for the duration of the study.
10. Participants who have been deemed inappropriate for participation based upon results from the Brief Symptoms Inventory (BSI-18) and discussions with the Principal Investigator and a study physician
11. Evaluation to sign consent form score \&lt;12.
12. MRI contraindications (excluding subjects who are pregnant, who have metal in any portion of their body, have medical complications, cardiac pacemaker, cochlear implant, aneurysm clip, certain IUDs, or known problems of claustrophobia).
13. Medications with common cognitive side-effects.
14. Bleeding disorders or platelet dysfunction (e.g., from regular aspirin usage).
15. Patients must not have any lesions in the lower motoneuron causing flaccid dysarthria.

Primary outcomes:
measure: Adverse Events
timeFrame: 29 days
measure: Discomfort and Pain
timeFrame: Baseline, 2 weeks, 4 weeks, 6 months.
Secondary outcomes:
measure: Dysphagia
timeFrame: 29 days
measure: Hand dexterity
timeFrame: 29 days.
measure: Muscle weakness
timeFrame: 29 days
measure: Dexterity of Articulation AMRs
timeFrame: 29 days
measure: Dexterity of Articulation SMRs
timeFrame: 29 days
measure: Intelligibility of Speech
timeFrame: 29 days
measure: Spasticity
timeFrame: 29 days
measure: Range of Motion (ROM)
timeFrame: 29 days
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Jorge Gonzalez-Martinez, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ho, J. et al. TARGETED DEEP BRAIN STIMULATION OF THE MOTOR THALAMUS FACILITATES VOLUNTARY MOTOR CONTROL AFTER CORTICO-SPINAL LESIONS. medRxiv 2023-03 (2023).
citation: Lozano AM, Lipsman N, Bergman H, Brown P, Chabardes S, Chang JW, Matthews K, McIntyre CC, Schlaepfer TE, Schulder M, Temel Y, Volkmann J, Krauss JK. Deep brain stimulation: current challenges and future directions. Nat Rev Neurol. 2019 Mar;15(3):148-160. doi: 10.1038/s41582-018-0128-2.
citation: Plow EB, Machado A. Invasive neurostimulation in stroke rehabilitation. Neurotherapeutics. 2014 Jul;11(3):572-82. doi: 10.1007/s13311-013-0245-y.
citation: Molnar GF, Sailer A, Gunraj CA, Cunic DI, Lang AE, Lozano AM, Moro E, Chen R. Changes in cortical excitability with thalamic deep brain stimulation. Neurology. 2005 Jun 14;64(11):1913-9. doi: 10.1212/01.WNL.0000163985.89444.DD.
citation: Baker KB, Plow EB, Nagel S, Rosenfeldt AB, Gopalakrishnan R, Clark C, Wyant A, Schroedel M, Ozinga J 4th, Davidson S, Hogue O, Floden D, Chen J, Ford PJ, Sankary L, Huang X, Cunningham DA, DiFilippo FP, Hu B, Jones SE, Bethoux F, Wolf SL, Chae J, Machado AG. Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial. Nat Med. 2023 Sep;29(9):2366-2374. doi: 10.1038/s41591-023-02507-0. Epub 2023 Aug 14.
citation: Cooper IS, Upton AR, Amin I. Reversibility of chronic neurologic deficits. Some effects of electrical stimulation of the thalamus and internal capsule in man. Appl Neurophysiol. 1980;43(3-5):244-58. doi: 10.1159/000102263.
citation: Phillips NI, Bhakta BB. Affect of deep brain stimulation on limb paresis after stroke. Lancet. 2000 Jul 15;356(9225):222-3. doi: 10.1016/s0140-6736(00)02487-9.
citation: Franzini A, Cordella R, Nazzi V, Broggi G. Long-term chronic stimulation of internal capsule in poststroke pain and spasticity. Case report, long-term results and review of the literature. Stereotact Funct Neurosurg. 2008;86(3):179-83. doi: 10.1159/000120431. Epub 2008 Mar 12.