Amygdala Insula Retraining in the Management of Multiple Sclerosis Symptoms

February 16, 2026 updated by: Chronic Conditions Research Fund

The goal of this study is to compare a lifestyle intervention and a mind-body intervention against a wait-list control in individuals with multiple sclerosis experiencing persistent symptoms.

Our research questions include:

Are lifestyle and mind-body interventions additive to usual care in MS?

Can these interventions improve MS symptoms and overall quality of life?

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Multiple sclerosis (MS) is a chronic, immune-mediated neurological condition characterized by inflammation and neurodegeneration within the central nervous system. Despite advances in disease-modifying therapies, many individuals with MS continue to experience persistent and disabling symptoms, including fatigue, cognitive dysfunction, pain, mood disturbance, autonomic dysregulation, sleep disruption, and reduced quality of life. These symptoms often fluctuate and may persist independent of inflammatory disease activity, underscoring the need for adjunctive, non-pharmacologic interventions that target symptom burden and functional outcomes.

This study evaluates two distinct educational interventions designed to support symptom management in individuals with MS: a comprehensive lifestyle education program and a neuroplasticity-based brain retraining program known as Amygdala and Insula Retraining (AIR). Lifestyle-focused interventions targeting stress management, nutrition, sleep, physical activity, and environmental exposures have demonstrated benefits across chronic illness populations and are increasingly recognized as important components of comprehensive MS care. In parallel, growing evidence supports the role of mind-body approaches in modulating autonomic nervous system function, stress, and measurable effects on fatigue, mood, pain, quality of life, and heart rate variability.

AIR is based on the principle that chronic illness and inflammatory stressors may sensitize neural circuits involved in threat detection and interoception, particularly the amygdala and insula, leading to persistent hypervigilance and maladaptive autonomic signaling. In MS, this heightened neural reactivity may contribute to symptom amplification such as increased fatigue, dysautonomia, and reduced stress resilience. AIR aims to de-sensitize these neural pathways through structured neuroplasticity-based cognitive and mindfulness practices, with the goal of interrupting maladaptive feedback loops and supporting improved autonomic and emotional regulation.

In this randomized pilot study, individuals with MS will be assigned to one of three groups: a lifestyle education program, the AIR program, or a wait-list control group. By comparing changes in validated symptom and quality-of-life measures across groups over time, this study aims to generate preliminary data on the feasibility and potential symptom-modifying effects of both interventions, informing the design of larger, controlled trials.

Study Type

Interventional

Enrollment (Actual)

132

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Iowa
      • Decorah, Iowa, United States, 52101
        • Luther College Department of Psychology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Confirmed multiple sclerosis diagnosis

Exclusion Criteria:

  • Previous experience with brain retaining programs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Experimental: Amygdala insula retraining
Mind body amygdala insula retraining intervention delivered virtually + usual care
Behavioral: Amygdala insula retraining
Mind body brain retraining intervention
Experimental: Lifestyle program
Mind body lifestyle intervention
Behavioral: Lifestyle program
Mind body lifestyle intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Fatigue Severity Scale
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Baseline (Week 0) to post-intervention (Week 12)

Secondary Outcome Measures

Outcome Measure
Time Frame
PROMIS Pain Interference 8a
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Baseline (Week 0) to post-intervention (Week 12)
EQ-5D (quality of life)
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Baseline (Week 0) to post-intervention (Week 12)
GAD-7 (anxiety)
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Baseline (Week 0) to post-intervention (Week 12)
PHQ-9 (depression, with suicidality item excluded)
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Baseline (Week 0) to post-intervention (Week 12)
MSQ-Revised (exploratory)
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Baseline (Week 0) to post-intervention (Week 12)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chronic Conditions Research Fund

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 15, 2024

Primary Completion (Actual)

March 15, 2025

Study Completion (Actual)

March 15, 2025

Study Registration Dates

First Submitted

February 16, 2026

First Submitted That Met QC Criteria

February 16, 2026

First Posted (Actual)

February 23, 2026

Study Record Updates

Last Update Posted (Actual)

February 23, 2026

Last Update Submitted That Met QC Criteria

February 16, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCRF-AIR-MS

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

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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