Validation of a Novel Cerebellar-striatal Satiety Circuit in Humans

This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study satiety in healthy individuals.

TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study, the investigators will be stimulating the brain to learn more about the role of the cerebellum in satiety.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Appetitive Behavior
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation (rTMS); Device: Sham repetitive Transcranial Magnetic Stimulation (rTMS)

Detailed Description

The purpose of this study is to conduct a circuit manipulation experiment to test the hypothesis that targeting the cerebellum can alter activity in response to food cues to advance the understanding of the involvement of the cerebellar-striatal circuit in feeding behavior.

Participants will undergo an initial screening session to complete informed consent and undergo baseline assessments including physical activity and food craving. Participants will additionally undergo an MRI scan that includes structural and resting-state functional magnetic resonance imaging (rsfMRI). These rsfMRI imagines will be used to isolate individual resting state networks for targeting of rTMS modulation.

Participants will then complete two separate testing sessions involving MRI imaging and food intake assessments before and after rTMS. One visit will involve consumption of a filling meal; the other visit will be completed following an overnight fast.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laura Holsen, PhD; Phone Number: 617-525-8772; Email: lholsen@bwh.harvard.edu
• Study Contact Backup: Name: Mark Halko, PhD; Phone Number: 617-855-2415; Email: mhalko@mclean.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital
      • Contact: Mark Halko, PhD; Phone Number: 617-855-2415; Email: mhalko@mclean.harvard.edu
    • Boston, Massachusetts, United States, 02120
      • Brigham and Women's Hospital
      • Contact: Laura Holsen, PhD; Phone Number: 617-525-8772; Email: lholsen@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy individuals aged 18 to 65
• BMI of 20-35.0 kg/m2
• Normal or corrected-to-normal vision
• Good general health
• Ability to understand and willingness to sign written informed consent document

Exclusion Criteria:

• Current and/or past medical conditions
• Current and/or past eating disorder
• On a restricted diet and/or taking weight loss medication(s)
• History of bariatric surgery
• Weight fluctuation >3% in past 3 months
• Recent history of illicit recreational drug abuse
• Current nicotine use
• Intellectual disability
• Conditions that might result in increased risks of side effects or complications from TMS or MRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active cerebellar rTMS; Cerebellar targeted iTBS	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); rTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry. Intermittent theta burst stimulation (iTBS) consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses (82), will be applied to the target. Cerebellar stimulation will be applied to the targets at 100% of aMT or 35% maximal stimulator output, whichever is higher.; Other Names: iTBS
Sham Comparator: Sham cerebellar rTMS; Cerebellar targeted sham iTBS	Device: Sham repetitive Transcranial Magnetic Stimulation (rTMS); rTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry. Intermittent theta burst stimulation (iTBS) consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses (82), will be applied to the target. Cerebellar stimulation will be applied to the targets at 100% of aMT or 35% maximal stimulator output, whichever is higher. Sham is achieved by using a coil with a magnetic shield preventing magnetic field from reaching the head.; Other Names: iTBS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in BOLD response in the cerebellum	Change in functional activation of the cerebellum will be assessed before (pre-TMS) and after (post-rTMS) rTMS stimulation, measured separately at the fed visit and at the fasted visit.	30 minutes pre-TMS and 30 minutes post-TMS, at each of two main study visits (fed, fasted)
Change in BOLD response in the ventral striatum	Change in functional activation of the ventral striatum will be assessed before (pre-TMS) and after (post-rTMS) rTMS stimulation, measured separately at the fed visit and at the fasted visit.	30 minutes pre-TMS and 30 minutes post-TMS, at each of two main study visits (fed, fasted)
Change in food reward valuation	Change in food reward valuation of high-calorie foods will be assessed using the Willingness to Pay task, measured before (pre-TMS) and after (post-rTMS) rTMS stimulation, measured separately at the fed visit and at the fasted visit.	up to 60 minutes pre-TMS and up to 60 minutes post-TMS, at each of two main study visits (fed, fasted)
Ad libitum snack food intake	Change in total caloric intake during the ad libitum snack food session will be assessed at the baseline visit and after (post-rTMS) rTMS stimulation, the latter measured separately at the fed visit and at the fasted visit.	baseline, up to 60 minutes post-TMS at each of two main study visits (fed, fasted)

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Beth Israel Deaconess Medical Center; Mclean Hospital
• Investigators: Principal Investigator: Laura Holsen, PhD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: October 19, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 2023P002811

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified participant data will be shared with NIMH Data Repository (NDA).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes