Dual Transcranial Direct Current Stimulation (dTDCS)-Enhanced Therapy After Hemorrhagic Strokes and VEGF

This study will evaluate the feasibility of dual tDCS to improve arm motor function in chronic stroke patients. In addition it will collect pilot data on the blood biomarkers associated with treatment effect.

Study Overview

• Status: Terminated
• Conditions: Hemorrhagic Stroke; Hemiparesis
• Intervention / Treatment: Device: dual transcranial direct current stimulation

Detailed Description

The proposed, increased intensity dtDCS is a new, economical, noninvasive stimulation approach that has the potential for large-scale clinical application. Dual tDCS, in conjunction with physical and occupational therapy, is not only more effective in enhancing motor performance and cortical plasticity compared to sham, but approximately 50% more effective than cathodal or anodal stimulation in healthy subjects and after stroke. However, it will only be clinically useful and important if the beneficial effects persist over time in a wider stroke patient population. Improvement in inter-hemispheric balance, through an activation shift toward the affected hemisphere and clinical improvement in response to tDCS has been reported previously in small studies. Hemorrhagic stroke patients have not been evaluated.

The investigators will study rehabilitation associated cortical plasticity at a cellular level to gain insight into the neural substrates underlying the clinical improvement. There are no prior studies investigating the potential of VEGF polymorphisms to contribute to rehabilitative treatment-induced functional recovery in humans. The investigators expect that patients with VEGF genotype 2578A/A will recover less then subjects without this polymorphism. Since in animal models VEGF and BDNF have a complimentary role, VEGF polymorphism may explain some of the variability in strength of association between BDNF polymorphism Val66Met and recovery. This novel pilot study measures both the genetic and physiologic expression of multiple growth factors - before and after a promising new therapy regimen - to better understand the contribution of growth factors to long-term plasticity and functional recovery. If VEGF serum levels elevate with clinical improvement, then this may identify a new indicator of treatment efficacy that can be collected noninvasively and with little cost. The results will provide guidance for new inclusion/exclusion criteria for clinical studies based on genetic markers, as well as uncover the potential for new therapeutic strategies to enhance treatment efficacy by augmenting VEGF during rehabilitation with FDA-approved strategies currently in clinical trials for other conditions (NIH Clinical Trials Registry: NCT01384162, NCT00620217, and NCT00744315).

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients (18-85 yo) with arm weakness (uFM <60) as a result of an ICH and no history of other neurologic or psychiatric illness that are able to activate wrist flexors (> MRC 1);
2. Patients with symptomatic ICH >5 months before enrollment;
3. Ashworth spasticity score <3.

Exclusion Criteria:

1. Patients with severe uncontrolled medical problems,
2. Patients with subarachnoid, subdural or epidural hemorrhage;
3. Patients with unstable cardiac arrhythmia;
4. Patients with contraindication to tDCS stimulation;
5. Patients who are not available for follow-up or unable to follow study procedures;
6. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dTDCS plus physical therapy; active dual transcranial direct current stimulation (TDCS) arm (M1-M1)	Device: dual transcranial direct current stimulation; Mild, non-invasive battery powered direct current applied to the head over the motor areas. No shaving or invasive procedures needed.; Other Names: dtDCS,; dual tDCS
Placebo Comparator: Sham dTDCS plus physical therapy; Non-effective dose dual TDCS stimulation arm, identical with intervention arm except for the stimulation intensity/duration used.	Device: dual transcranial direct current stimulation; Mild, non-invasive battery powered direct current applied to the head over the motor areas. No shaving or invasive procedures needed.; Other Names: dtDCS,; dual tDCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	any adverse events that might be related to study procedures	enrollment to 3 month followup
Upper Extremity Fugl-Meyer Score	Upper extremity motor impairment scale. Scale ranges from 0 (worst, can not perform any tasks) to 66 ( performs all tasks fully).	change between before and 3 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wolf Motor Function Test	Timed performance of 15 functional upper extremity tasks, 0-120 seconds, and 2 strength measures. WMFT time measurements are calculated as the arithmetic mean of rate of performance, where we calculate "how many times would a person have completed the task, had he or she been performing it continuously for 60 seconds". Therefore the results have a minimum score of 0, where the subject could not perform any of the tasks, and no pre-defined maximum score, the higher the rate score the faster the subject was able to perform the tasks. ( see Hodics et al.,2013)	change between before and at 3 months follow-up

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: American Heart Association

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): April 17, 2017

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: February 25, 2019
• First Posted (Actual): February 27, 2019

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Stroke; Hemorrhagic Stroke; Paresis
• Other Study ID Numbers: 14GRNT18690039; STU 012014-028 (Other Identifier: IRB University of Texas Southwestern Medical Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No