REM Sleep Disruption and Its Potential Uses in Depression Management

NCT07891806 | Completed

• 2 other identifiers: #2024-241218-002SMIS 308944
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 2

Brief Summary

This randomized study evaluated whether brief wrist vibrations delivered through an Apple Watch during algorithm-identified rapid eye movement (REM) sleep could reduce depressive symptoms over approximately four weeks. Adults with clinically significant depressive symptoms were assigned to either REM-contingent haptic stimulation or a monitoring-only control condition. Both groups used the same iPhone and Apple Watch applications and received the same morning Smart Alarm function; only the intervention group received night-time haptic stimulation during probable REM sleep. Sleep stages were estimated in real time using wrist accelerometry and photoplethysmography. Depressive symptoms were assessed using clinician-rated and self-reported measures, with the Montgomery-Åsberg Depression Rating Scale (MADRS) as the primary clinical outcome and the Beck Depression Inventory-II (BDI-II) as a secondary outcome. Sleep architecture, treatment exposure, adherence, and tolerability were also evaluated.

Conditions

Depression / Major Depressive Disorder; Depressed Mood

Keywords

REM sleep; depression; wearable devices; haptic stimulation; digital therapeutics; randomized controlled trial; sleep architecture

Outcome Measures

Primary Outcomes (1)

• Final Montgomery-Åsberg Depression Rating Scale (MADRS) Score

  Clinician-rated depressive symptom severity measured using the Montgomery-Åsberg Depression Rating Scale (MADRS). The primary analysis compared final MADRS scores between the experimental and control groups using analysis of covariance (ANCOVA), adjusted for baseline MADRS score. Lower MADRS scores indicate lower depressive symptom severity.

  Baseline and final post-intervention assessment, within 40 days after completion of the intervention.

Study Arms (2)

REM-Contingent Haptic Stimulation

EXPERIMENTAL

Participants used the study iPhone and Apple Watch applications for sleep monitoring and received REM-contingent vibrotactile stimulation during algorithm-identified probable REM sleep. Sleep stage was estimated in real time from wrist accelerometry and photoplethysmography. A morning Smart Alarm haptic function was also available, as in the Control arm.

Device: REM-Contingent Smartwatch Haptic Stimulation; Device: Smartwatch Sleep Monitoring and Smart Alarm

Monitoring-Only Control

OTHER

Participants used the same study iPhone and Apple Watch applications for sleep monitoring but did not receive REM-contingent night-time haptic stimulation. The same morning Smart Alarm haptic function available to the Experimental arm was also available in this group.

Device: Smartwatch Sleep Monitoring and Smart Alarm

Interventions

REM-Contingent Smartwatch Haptic Stimulation DEVICE

A pre-release iOS/watchOS system used Apple Watch accelerometry and photoplethysmography to classify consecutive 30-second epochs as wake, REM sleep, or non-REM sleep. In the experimental arm, two consecutive epochs classified as REM triggered wrist-delivered vibrotactile stimulation. Predefined haptic patterns included REM Shift L (2 Hz for 7 seconds, with a 20-second extended variant) and REM Shift M (2 Hz for 15 seconds). After each cue, the following sleep-stage estimate was reassessed; if REM persisted, additional stimulation could be delivered for up to five sets, followed by a minimum 10-minute suspension period. Stimulation was not delivered when the participant was classified as awake.

REM-Contingent Haptic Stimulation

Smartwatch Sleep Monitoring and Smart Alarm DEVICE

Participants in both study groups used the same pre-release iOS application and watchOS companion application for nocturnal sleep monitoring. The system collected wrist accelerometry and photoplethysmography data and generated algorithm-based sleep-stage estimates. A morning Smart Alarm was enabled by default in both groups and delivered a brief wrist haptic nudge consisting of click-type pulses at 2 Hz for 5 seconds.

Monitoring-Only Control; REM-Contingent Haptic Stimulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years, inclusive; all genders.
• Apple ecosystem user, with iPhone as the minimum requirement.
• Clinical diagnosis of depression/major depressive disorder or clinician administered MADRS score at least 8.
• Signed informed consent.

You may not qualify if:

• Use of any other medication considered likely to interact with REM sleep.
• Presence of another relevant psychiatric or psychological disorder, including schizophrenia, other affective disorders, substance abuse/addiction, dementia, PTSD, or another clinically relevant disorder.
• Epilepsy.
• Chronic debilitating disease, including significant cardiac, pulmonary, hepatic, or renal disease.
• Known diagnosis of obstructive sleep apnea, REM sleep behavior disorder, or narcolepsy.
• Regular circadian-rhythm disruption, including shift work or treatment interfering with circadian rhythm or sleep cycles, such as prazosin.

Sponsors & Collaborators

• WAKEZ HEALTH TECH ECOSYSTEM SRL: lead
• Emergency County Hospital Cluj-Napoca: collaborator

Study Sites (2)

County Emergency Clinical Hospital Cluj-Napoca

Cluj-Napoca, Romania

Location

WakeZ Health Tech Ecosystem SRL

Cluj-Napoca, Romania

Location

MeSH Terms

Conditions

Depression; Depressive Disorder, Major; Consciousness Disorders

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2026
• First Posted: October 23, 2026
• Study Start: September 1, 2025
• Primary Completion: November 30, 2025
• Study Completion: November 30, 2025
• Last Updated: October 23, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: Beginning upon publication of the primary study results and remaining available for as long as the supplementary materials accompanying the publication remain publicly accessible.
• Access Criteria: De-identified individual participant data underlying the primary and secondary clinical outcomes will be made publicly available as supplementary material accompanying the primary publication. No additional approval or data-use agreement will be required to access these data. Additional non-public study data will not be included in this sharing plan.

Locations

RO (2)