Menopausal Complaints, Perimenopause
Conditions
Keywords
Amygdala and Insula Retraining (AIR)
Brief summary
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?
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.
Interventions
BEHAVIORALAmygdala and Insula Retraining (AIR)
Mind-body brain retraining intervention
Sponsors
Chronic Conditions Research Fund
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is a 24-week, parallel-group, randomized, wait-list-controlled trial conducted remotely. A minimum of 160 perimenopausal and early postmenopausal 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.
Eligibility
Sex/Gender
FEMALE
Age
38 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Experiencing perimenopausal symptoms * Meets STRAW+10 criteria based on self-assessment (-2 to +1c) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Menopause Rating Scale (MRS) Total Score | Baseline (Week 0) to post-intervention (Week 12) | Overall perimenopausal symptom burden as measured by the Menopause Rating Scale (MRS). Scale: none (0)/extremely severe (4) - higher means worse outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Greene Climacteric Scale | Baseline (Week 0) to post-intervention (Week 12) | Overall climacteric symptom severity. Scale: not at all (0)/extremely (3) - higher means worse outcome |
| Hot Flash Related Daily Interference Scale (HFRDIS) | Baseline (Week 0) to post-intervention (Week 12) | Impact of vasomotor symptoms on daily functioning. Scale: do not interfere (0)/completely interfere (10) - higher means worse outcome |
| Insomnia Severity Index (ISI) | Baseline (Week 0) to post-intervention (Week 12) | Subjective sleep disturbance and insomnia severity. Scale: none (0)/very (4) - higher means worse outcome. |
| PROMIS Fatigue Short Form 8a | Baseline (Week 0) to post-intervention (Week 12) | Fatigue severity and impact. Scale: not at all or never (33)/ very much or always (78) - higher means worse outcome |
| Patient Health Questionnaire-9 (PHQ-9) | Baseline (Week 0) to post-intervention (Week 12) | Depressive symptoms. Scale: not at all (0)/nearly every day (3) and not difficult at all/extremely difficult - higher means worse outcome |
| Generalized Anxiety Disorder-7 (GAD-7) | Baseline (Week 0) to post-intervention (Week 12) | Anxiety symptoms. Scale: Not at all (0)/nearly every day (3) and not difficult at all/extremely difficult - higher means worse outcome |
| Patient Global Impression of Change (PGIC) | Assessed at Weeks 12 and 24 | Overall perceived improvement |
| Female Sexual Function Index (FSFI) | Baseline (Week 0) to post-intervention (Week 12) (optional) | Sexual function (optional). Scale: 2.0/36.0 - higher means better outcome |
Countries
United States
Outcome results
None listed