Amygdala Insula Retraining in the Management of Perimenopause Symptoms

February 16, 2026 updated by: Chronic Conditions Research Fund

The goal of this study is to evaluate a neuroplasticity-based mind-body intervention, Amygdala and Insula Retraining (AIR), compared to a wait-list control in individuals experiencing perimenopausal symptoms.

Our research questions include:

Does AIR reduce overall perimenopausal symptom burden compared to a wait-list control?

Does AIR improve sleep disturbance, vasomotor symptom interference, fatigue, mood, anxiety, and quality of life in perimenopausal individuals?

Are symptom changes associated with improvements in autonomic regulation and sleep parameters, as reflected by exploratory wearable measures including heart rate variability?

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Perimenopause is a transitional reproductive stage marked by fluctuations in ovarian steroid hormones. It is often associated with sleep disruption, fatigue, mood changes, anxiety, cognitive changes, and diminished quality of life. Emerging evidence suggests that, in addition to hormonal changes, alterations in central threat processing, interoception, and autonomic nervous system regulation may contribute to symptom amplification and persistence during this period.

Amygdala and Insula Retraining (AIR) is a structured, neuroplasticity-based behavioral intervention designed to modulate the autonomic nervous system. The program integrates cognitive reframing, somatic retraining, mindfulness practices, breathwork, behavioral pattern interruption, and safety-signal conditioning with the aim of calming hyper-reactive limbic pathways. Through repeated practice, AIR seeks to restore autonomic balance and reduce symptom burden.

This study is a 24-week, parallel-group, randomized, wait-list-controlled trial conducted remotely. A minimum of 160 perimenopausal participants aged 38 to 60 years will be randomized in a 1:1 ratio to either an active intervention arm or a wait-list control arm. Participants in the active intervention arm will receive immediate access to the 12-week AIR program in addition to treatment as usual. Participants in the wait-list control arm will continue treatment as usual for 12 weeks and will receive access to the recorded AIR intervention following completion of the primary endpoint assessment. Both groups will be followed through week 24.

The primary assessment is the the Menopause Rating Scale (MRS) total score from baseline (T0) to post-intervention at week 12 (T1). Secondary outcomes, assessed at baseline, week 12, and week 24, include insomnia severity, fatigue, anxiety, depression, patient global impression of change, and sexual function (optional). Concomitant therapies, including hormone replacement therapy and relevant medications, will be recorded at all assessment time points.

An exploratory wearable sub-study will be conducted in a randomly selected subset of approximately 50 participants distributed across both study arms. Wearable devices will be used to collect objective physiological measures, including heart rate variability, resting heart rate, sleep duration and efficiency, and activity metrics. These data will be analyzed descriptively to explore potential physiological correlates of symptom change.

Study Type

Interventional

Enrollment (Estimated)

160

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

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Experiencing perimenopausal symptoms
  • Meets STRAW+10 criteria based on self-assessment
  • Able to read and understand English
  • Access to internet

Exclusion Criteria:

  • Pregnancy
  • Presence of a severe psychiatric condition requiring immediate clinical intervention
  • Uncontrolled thyroid disease or prolactinoma
  • Active cancer treatment
  • Inability to provide informed consent
  • Any medical or psychiatric condition that, in the judgment of the investigator or study team, would interfere with safe participation or study completion

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
Experimental: Amygdala insula retraining
Participants receive immediate access to the 12-week Amygdala and Insula Retraining (AIR) program in addition to treatment as usual.
Behavioral: Amygdala and Insula Retraining (AIR)
Mind-body brain retraining intervention
No Intervention: Control
Participants receive treatment as usual for 12 weeks and are offered access to the Amygdala and Insula Retraining (AIR) program after completion of the primary outcome assessment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Menopause Rating Scale (MRS) Total Score
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Overall perimenopausal symptom burden as measured by the Menopause Rating Scale (MRS)
Baseline (Week 0) to post-intervention (Week 12)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Greene Climacteric Scale
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Overall climacteric symptom severity
Baseline (Week 0) to post-intervention (Week 12)
Hot Flash Related Daily Interference Scale (HFRDIS)
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Impact of vasomotor symptoms on daily functioning
Baseline (Week 0) to post-intervention (Week 12)
Insomnia Severity Index (ISI)
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Subjective sleep disturbance and insomnia severity
Baseline (Week 0) to post-intervention (Week 12)
PROMIS Fatigue Short Form 8a
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Fatigue severity and impact
Baseline (Week 0) to post-intervention (Week 12)
Patient Health Questionnaire-9 (PHQ-9)
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Depressive symptoms
Baseline (Week 0) to post-intervention (Week 12)
Generalized Anxiety Disorder-7 (GAD-7)
Time Frame: Baseline (Week 0) to post-intervention (Week 12)
Anxiety symptoms
Baseline (Week 0) to post-intervention (Week 12)
Patient Global Impression of Change (PGIC)
Time Frame: Assessed at Weeks 12 and 24
Overall perceived improvement
Assessed at Weeks 12 and 24
Female Sexual Function Index (FSFI)
Time Frame: Baseline (Week 0) to post-intervention (Week 12) (optional)
Sexual function (optional)
Baseline (Week 0) to post-intervention (Week 12) (optional)

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 (Estimated)

March 1, 2026

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2026

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

Other Study ID Numbers

  • CCRF-AIR-PM

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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