tDCS and Glucose Uptake in Leg Muscles

Transcranial Direct Current Stimulation to Reduce Asymmetric Glucose Uptake in Leg Muscles of Persons With Multiple Sclerosis

This study is to examine the efficacy of tDCS to improving walking in people with Multiple Sclerosis (PwMS).

Our study compromises 1 group of subjects with MS which will attend the lab for three sessions. In the first session, subjects will be consented, complete the Patient Determined Disease Steps (PDDS), the Fatigue Severity Scale (FSS), and maximal voluntary contractions (MVCs) of the right and left knee extensors and flexors to determine the more-affected leg. The second and third sessions will involve whole-body FDG PET imaging. During each of these sessions, the subject will walk for 20 min on a treadmill at a self-selected speed during which time tDCS or SHAM, in a blinded manner, will be applied to the motor cortex (M1) corresponding to the more-affected leg. Approximately 2 minutes into the walking, [18F]fluorodeoxyglucose (FDG) will be administered by IV injection. Immediately after the walking is completed, the subject will be positioned in the PET/CT scanner and a whole body (top of head to toes) PET/CT scan will be acquired for the evaluation of glucose metabolism in the brain, spine, and lower extremities. The third session will be identical to the second session with the exception that the opposite condition (tDCS or SHAM) will be used.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Device: transcranial direct current stimulation or SHAM

Detailed Description

Prospective participants, men and women with MS, will be recruited. The plan is to enroll up to 30 to get 20 evaluable subjects. To accomplish this study, all participants will need to complete 3 sessions. The first session at the INPL and sessions 2 and 3 at PET Imaging Center (0911ZJPP) and the PET Imaging lab in Pappajohn Biomedical Discovery Building. Session 2 and 3 are separated by 5-8 days. The duration of each session will be approximately 120 minutes. We expect data collection to last 6 months.

In the first session, subjects will be consented, complete the PDDS, the Fatigue Severity Scale (FSS), and maximal voluntary contractions (MVCs) of the right and left knee extensors and flexors to determine the more-affected leg. When leg strength difference is less than 10%, the more affected side will be based on self-report. The second and the third sessions will involve 20 min walking on a treadmill at a self-selected speed during which time tDCS or SHAM will be applied to the motor cortex (M1) corresponding to the more-affected leg and [18F]fluorodeoxyglucose will be administered. At the end of the walking period, the subject will be imaged on a PET/CT scanner from top of head to toes.

Prior to sessions 2 and 3, all subjects will be asked to fast (water and medication can be taken during this time) for a minimum of 6 hours prior to the FDG administration. In addition, the blood glucose level will be checked (via Accuchek) prior to FDG administration and the level must be equal to or less than 200 mg/dL in order to proceed with the FDG administration on that day. At the beginning of session 2 and 3, the subject will be weighed and height measured, have a blood glucose level determined via Accuchek as described above, undergo a urine pregnancy test if the subject is of child-bearing potential, and have an IV catheter inserted for FDG administration. The subject will then be moved to the PET Scanner area in Pappajohn Biomedical Discovery Building. The subject will be asked to use the restroom prior to walking on the treadmill. A tDCS device (Soterix) will deliver a small direct current through two sponge surface electrodes (5cm × 5cm, soaked with 15 mM NaCl). The positive electrode will be placed over the motor cortex representation of the more affected leg, and a second electrode will be placed on the forehead above the contralateral orbit. The participant will receive tDCS or SHAM throughout the walking (i.e., for 20 min). In the tDCS trial, the intensity will start at 0 mA and will increase to 3 mA over the first 30 seconds. In the sham condition, the participants will receive the initial 30 seconds of stimulation, after which the current will be set to 0.

Two min into the walking test on the treadmill, 10 mCi of [18F]-FDG will be injected IV. Then, the walking test continues until 20 min is reached. When the walking test is completed, the tDCS device will be removed and the subject will be positioned in the PET/CT scanner and a whole body (top of head to toes) PET/CT scan will be acquired.

Ratings of perceived exertion (RPE) will be recorded with the modified Borg 10-point scale (Borg, 1982). The subjects will be instructed to estimate the effort during walking. The scale will be anchored so that 0 denotes the resting state and 10 represents the strongest effort.

No long-term follow-up will be done.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• medically diagnosed with Multiple Sclerosis (MS)
• 18-70 yrs. of age, moderate disability (Patient Determined Disease Steps (PDDS) core 2-6)
• Self-reported differences in function between legs, able to walk for 20 min.

Exclusion Criteria:

• MS relapse within last 60 days
• inability to fast for 6 hours
• hyperglycemia (fasting blood sugar > 200 mg/dL)
• insulin-dependent diabetes
• high risk for cardiovascular disease (ACSM risk classification)
• changes in disease-modifying medications within last 45 days
• concurrent neurological/neuromuscular disease
• hospitalization within last 90 days
• diagnosed depression
• inability to understand/sign informed consent, pregnant, history of seizure disorders (or on medications known to lower seizure threshold)
• hydrocephalus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: tDCS first then SHAM effects on glucose uptake in leg muscles; tDCS Block: The subject will walk for 20 min on a treadmill at a self-selected speed during which time tDCS will be applied to the motor cortex (M1) corresponding to the more-affected leg. Sham Block: The subject will walk for 20 min on a treadmill at a self-selected speed during which time SHAM will be applied to the motor cortex (M1) corresponding to the more-affected leg.

Device: transcranial direct current stimulation or SHAM; A tDCS device (Soterix) will deliver a small direct current through two sponge surface electrodes (5cm × 5cm, soaked with 15 mM NaCL). The positive electrode will be placed over the motor cortex representation of the more affected leg, and a second electrode will be placed on the forehead above the contralateral orbit. In the sham condition, the participants will receive the initial 30 seconds of stimulation, after which the current will be set to 0. The same tDCS device (Soterix) will be used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose Uptake in Leg Muscles	Participants are walking on a treadmill with tDCS or SHAM, followed by a positron emission tomography (PET) scan to measure glucose uptake in leg muscles. SUV asymmetry indices (AIs) were calculated to determine the magnitude of asymmetry between the more- and less-affected legs with a previously used equation: ((less-affected side - more-affected side)/((0.5) × (less-affected side + more- affected side)) × 100). An AI value ≥ 10% was considered asymmetric.	Six Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratings of Perceived Exertion (RPE)	Ratings of perceived exertion (RPE) will be recorded with the modified Borg 10-point scale (Borg, 1982). The subjects will be instructed to estimate their effort during walking. The scale will be anchored so that 0 denotes the resting state and 10 represents the strongest effort they are able to perform.	Six Months

Collaborators and Investigators

• Sponsor: University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2019
• Primary Completion (Actual): October 1, 2020
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 12, 2019

Study Record Updates

• Last Update Posted (Actual): January 25, 2023
• Last Update Submitted That Met QC Criteria: January 2, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: tDCS; PET; Multiple Scerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 201905825

Plan for Individual participant data (IPD)

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

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