Deep Brain Stimulation Motor Ventral Thalamus (VOP/VIM) for Restoration of Speech and Upper-limb Function in People With Subcortical Stroke

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular Diseases; Stroke; Central Nervous System Diseases; Nervous System Diseases; Brain Disease
• Intervention / Treatment: Device: Deep Brain Stimulation (DBS) of the Motor Thalamus

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cierra Clark, MS; Phone Number: 240-441-4216; Email: cic27@pitt.edu
• Study Contact Backup: Name: Elvira Pirondini, PhD; Phone Number: 412-636-0595; Email: elvirap@pitt.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
      • Contact: Cierra Clark, MS; Phone Number: 240-441-4216; Email: cic27@pitt.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 70 years old. (Participants outside this age range may be at an increased medical risk and have an increased risk of fatigue during testing).
3. Native English speaker.
4. Patients with moderate to severe dysarthria (50-89% intelligibility in the Assessment of Intelligibility of Dysarthric Speech test).

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 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 the 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 <12.
12. MRI contraindications (excluding subjects who are pregnant, who have metal in any portion of the 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. Hypersensitivity to barium sulfate (for barium swallow test)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Deep Brain Stimulation of the Motor Thalamus; Individuals who have speech and motor deficits due to a stroke.

Device: Deep Brain Stimulation (DBS) of the Motor Thalamus; All participants enrolled in this group 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	The investigators will quantify the safety of DBS to treat post-stroke speech and upper-limb motor deficits. For this, the investigators will record all adverse events for the entire study duration. The study is considered successful if no serious adverse events related to the use of deep brain stimulation are reported.	29 days
Discomfort and Pain	The investigators will assess the relative level of discomfort and/or pain that is associated with the delivery of electrical stimulation to the motor thalamus. After each stimulation train patients will be asked to report a level of perceived discomfort using a 10 value subjective scale. Low values will be assigned to low discomfort and high values to high discomfort. The study is considered successful if 70% of recruited subjects do not report discomfort or pain at stimulation amplitudes that are required to obtain motor responses in the face and upper-limb muscles.	Baseline, 2 weeks, 4 weeks, 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dysphagia	The investigators will use the modified barium swallow study (MBSS) to assess oropharyngeal swallow functions. This is a performance evaluation scale, that consist of 17 items with varying scales. The total score ranges from 0 to 55, where a higher score means a better outcome. Based on the preliminary data, the investigators will consider an increase of 1 point in at least 50% of the items of the Modified Barium Swallow Impairment Profile as a minimally acceptable improvement in swallow functions.	29 days
Hand dexterity	The investigators will use the Box and Blocks Test to measure hand dexterity ability. Based on the preliminary data, the investigators will consider a percentage change of 18% as a minimally acceptable improvement in hand dexterity.	29 days.
Muscle weakness	The investigators will measure muscle strength and range of motion produced by the subject during isometric facial movements (e.g. smile, tongue out, puckered lips, and open-close mouth). Based on the preliminary data, the investigators will consider an increase of 50% in ROM as a minimally acceptable improvement in muscle strength.	29 days
Dexterity of Articulation AMRs	The investigators will measure dexterity of articulation by alternating motion rates (AMRs) of the repetitive plosive sound (pah, tah, and kah). The investigators will consider an improvement of 10% in the rate to be minimally acceptable.	29 days
Dexterity of Articulation SMRs	The investigators will measure dexterity of articulation by sequential motion rates (SMRs) of the repetitive plosive sound (pah, tah, and kah). The investigators will consider an improvement of 10% in the rate to be minimally acceptable.	29 days
Intelligibility of Speech	The investigators will use the Assessment of Intelligibility of Dysarthric Speech (AIDS) to assess the quality of communication and intelligibility of speech at both word- and sentence-level. The investigators will consider an improvement of 5% correctly transcribed to be minimally acceptable.	29 days
Spasticity	Spastic dysarthria is characterized by a higher fundamental frequency (F0) of phoneme utterances than what is seen in normal speech. Thus, the investigators will quantify the degree of spasticity by calculating the F0 across a series of phonemes. The investigators will consider a reduction in F0 of 20% to be minimally acceptable.	29 days
Range of Motion (ROM)	The investigators will use the 2nd Edition Frenchay Dysarthria Assessment (FDA-2) to measure patterns of oral motor functions, with a particular focus on the following subsections: Respiration, Lips, Palate, Laryngeal, and Tongue. Each subsection is rated on a scale from "a" to "e", where "a" means normal for age, and "e" means unable to undertake task/movement/sound. So a score closer to "a" means a better outcome. The investigators will consider an improvement in severity level (e.g., from considerable to moderate severity, or a score of D to C) to be minimally acceptable.	29 days

Collaborators and Investigators

• Sponsor: Jorge Gonzalez-Martinez
• Investigators: Principal Investigator: Jorge Gonzalez-Martinez, MD/PhD, University of Pittsburgh

Publications and helpful links

General Publications

• Ho, J. et al. TARGETED DEEP BRAIN STIMULATION OF THE MOTOR THALAMUS FACILITATES VOLUNTARY MOTOR CONTROL AFTER CORTICO-SPINAL LESIONS. medRxiv 2023-03 (2023).
• 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.
• Plow EB, Machado A. Invasive neurostimulation in stroke rehabilitation. Neurotherapeutics. 2014 Jul;11(3):572-82. doi: 10.1007/s13311-013-0245-y.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cerebrovascular Disorders; Stroke; Cardiovascular Diseases; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases
• Other Study ID Numbers: STUDY22070043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data may be shared with other researchers for the purpose of data analysis and collaboration.
• IPD Sharing Time Frame: Data will become available at the end of the trial upon publication of the first manuscript. Estimation is 2 years from enrollment of the first participant.
• IPD Sharing Access Criteria: Data must be directly requested from the PI and will be shared upon completion of the necessary data-sharing agreement to protect confidential patient information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No