Intra-Sessional Autonomic Arc Detection in Ketamine-Assisted Therapy for PTSD: A Signal Characterisation Pilot Study (OMS-KAT)

Intra-Sessional Autonomic Arc Detection Using Continuous HRV and EDA Monitoring in Adults Undergoing Ketamine-Assisted Therapy for PTSD: A Prospective Observational Signal Characterisation Pilot Study

This study examines whether a continuous wearable biosensor and a proprietary signal detection algorithm (JungleCODE, Open Medicine Studio) can detect and characterise the autonomic nervous system arc - a trajectory from a state of high physiological arousal (aporia) to a state of regulated calm (ataraxia) - during ketamine-assisted therapy (KAT) sessions in adults with post-traumatic stress disorder (PTSD).

Participants independently arrange their own ketamine-assisted therapy sessions with a licensed British Columbia provider. The researcher does not administer ketamine or any other substance. The researcher's role is continuous physiological monitoring via a wrist-worn biosensor (EmbracePlus, Empatica) and a structured post-session interview only.

The primary purpose is to determine whether the JungleCODE arc-position detection algorithm can identify a consistent, characterisable autonomic trajectory within KAT sessions, and to assess the feasibility of this monitoring protocol. This is a pilot signal characterisation study (N=2-6); no therapeutic outcomes are assessed and no clinical claims are made.

Study Overview

• Status: Not yet recruiting
• Conditions: Post-Traumatic Stress Disorder
• Intervention / Treatment: Device: Continuous wearable physiological monitoring (EmbracePlus, Empatica); Drug: Ketamine-assisted therapy (independently arranged); Other: Structured pre- and post-session interviews

Detailed Description

Post-traumatic stress disorder (PTSD) affects an estimated 9.2% of Canadians over a lifetime, with particularly high prevalence among first responders, veterans, and survivors of interpersonal violence. Conventional first-line treatments leave a significant proportion of patients with residual symptoms, and access to evidence-based care remains limited in rural and remote settings. Ketamine-assisted therapy (KAT) has demonstrated rapid anxiolytic and antidepressant effects in multiple randomised controlled trials and represents a promising approach for treatment-refractory PTSD. However, the mechanisms through which KAT produces therapeutic change, and the conditions that determine whether a given session produces durable benefit, are incompletely understood.

The REBUS (Relaxed Beliefs Under Psychedelics) account provides the theoretical foundation for this study. Under this framework, ketamine temporarily reduces the precision-weighting of high-confidence predictive priors - including deeply entrenched trauma-related threat appraisals - creating a window of increased neuroplasticity during which the generative model is most available for revision. This window is hypothesised to correspond to a specific autonomic configuration: a shift from peak sympathetic activation toward increasing ventral vagal dominance, characterised by falling electrodermal activity, rising HRV coherence, and emerging parasympathetic predominance. This configuration is referred to as the Transition Window. The Transition Window is theoretically critical because articulation of psychological content delivered during this state is predicted to produce genuine prior-precision reduction, whereas identical articulation delivered outside this window is predicted to produce verbal acknowledgement without the underlying autonomic reorganisation that constitutes genuine release.

The foundational challenge for testing this prediction empirically is that no validated method has existed for detecting the Transition Window in real time. This study addresses that gap by applying the JungleCODE arc-position detection algorithm to continuous intra-sessional physiological data from KAT participants.

JungleCODE (Open Medicine Studio; patent pending, PCT filed) is a proprietary signal processing algorithm that analyses continuous heart rate variability (HRV) time-series data - and, where available, electrodermal activity (EDA) - to estimate arc position on a clinically defined aporia-to-ataraxia spectrum. Aporia refers to the state of peak arousal, maximal predictive prior precision, and high sympathetic drive. Ataraxia refers to the state of regulatory restoration, reduced prior precision, and ventral vagal dominance. Unlike single-biomarker threshold approaches, JungleCODE is a trajectory detection algorithm: it identifies where in a continuous arc the person is located based on the directional pattern of change over time, not the absolute value at any given moment. The algorithm outputs arc-position scores at 30-second intervals along with transition event flags, trajectory classification, and autonomic phase designation.

This study is observational and non-interventional. Participants independently arrange their own ketamine-assisted therapy sessions with a licensed British Columbia physician or nurse practitioner. The researcher does not administer ketamine or any other substance and has no clinical role during the session. All clinical decisions and safety oversight during the KAT session remain entirely with the licensed treating provider. The researcher's role is continuous physiological monitoring via an EmbracePlus wrist-worn wearable biosensor and a structured post-session interview.

The EmbracePlus (Empatica Inc.) is a medical-grade research biosensor that records the interbeat interval stream at 64 Hz, EDA phasic and tonic components, skin temperature, and accelerometry. Data is streamed via Bluetooth to a secured local device and transferred to the Open Medicine Studio sovereign data layer - a self-managed, physician-controlled PostgreSQL database hosted in AWS ca-central-1, encrypted at rest using physician-held customer-managed keys - within 24 hours of each monitoring session.

The study proceeds across three phases for each participant. The preparation phase, conducted three to seven days before the KAT session, establishes the participant's individual arc baseline through continuous wearable monitoring during normal daily activity and sleep. A structured pre-session interview, audio-recorded with participant consent, is conducted within 48 hours of the session. The intra-sessional phase involves continuous EmbracePlus monitoring throughout the KAT session, from preparation through dosing to immediate integration onset. The researcher is not present at the session site unless explicitly invited by the treating provider; where present, the researcher acts solely as an observer and has no clinical role. Precise session timestamps are recorded to enable temporal mapping of arc-position events onto session phases. The integration phase involves three to five day wearable monitoring windows at one, two, and four weeks post-session, with brief structured check-in interviews and administration of the PCL-5 at two and four weeks.

The primary outcome is characterisation of the intra-sessional autonomic arc trajectory - including arc depth, inflection timing, transition event identification, and trajectory classification - as detected by the JungleCODE algorithm applied to the continuous EmbracePlus data stream. Secondary outcomes include the temporal correspondence between arc-position transition events and KAT session phase timestamps, the integration-phase arc trajectory compared to individual pre-session baseline, and the correspondence between arc-position transition event timing and participant-reported subjective experience assessed via the Post-Session Subjective Integration Scale. PTSD symptom severity as measured by PCL-5 is collected as an exploratory measure; this pilot study is not powered to assess symptom outcomes.

This is a pilot signal characterisation study with a target enrolment of two to six participants. No hypothesis tests are pre-specified. Analysis is descriptive, focused on arc trajectory visualisation, transition event identification, and feasibility metrics including device wear compliance, data quality, and participant retention. The findings will be used to calibrate the JungleCODE algorithm for the KAT context, characterise inter-individual variability in arc trajectory parameters, and identify candidate arc-event signatures for subsequent hypothesis testing in larger controlled trials.

All data is governed by the Open Medicine Studio Sovereign Data Management Blueprint (JC-DMB-001 v1.0) and is held in compliance with the BC Personal Information Protection Act (PIPA) and the federal Personal Information Protection and Electronic Documents Act (PIPEDA). Participants are assigned pseudonymous codes at enrolment; the linkage list is held by the PI on an encrypted offline device separate from all study data. No identifiable data is stored in or transmitted to any third-party system.

Ethics oversight is provided by the Canadian SHIELD Ethics Review Board (CSERB; OHRP Registration IORG0003491; FDA Registration IRB00004157). The study is registered on ClinicalTrials.gov prior to enrolment of the first participant, consistent with ICMJE requirements.

• Study Type: Observational
• Enrollment (Estimated): 5

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Ganges, British Columbia, Canada, V8K 1R1
      • Open Medicine Studio
      • Contact: Adriaan D van der Wart, MBChB; Phone Number: 7789513194; Email: doctor@medicinestudio.com
      • Contact: Natalie Moore; Phone Number: +1 4165756565; Email: natalie@openmedicinestudio.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults aged 19 years or older with a current or previous diagnosis of post-traumatic stress disorder confirmed by CAPS-5 clinical assessment (score 23 or higher), who have independently arranged a ketamine-assisted therapy session with a licensed physician or nurse practitioner in British Columbia, Canada. Participants are recruited through referrals from licensed ketamine-assisted therapy providers in British Columbia. This is a non-probability convenience sample consistent with the pilot and signal characterisation purpose of the study. No healthy volunteers are enrolled.

Description

Inclusion Criteria:

1. Adults aged 19 to 65 years
2. Currently enrolled in or referred for equine-assisted therapy at the study facility
3. No prior relationship with the therapy horse assigned to their study sessions
4. Able to wear a chest-strap heart rate monitor comfortably for 35 minutes
5. Able to provide written informed consent in English
6. Willing to have sessions video recorded for research purposes

Exclusion Criteria:

1. Diagnosed cardiac arrhythmia of any type
2. Implanted cardiac device including pacemaker or implantable cardioverter-defibrillator
3. Current use of beta-blockers, calcium channel blockers, digoxin, or any other medication known to suppress or significantly alter heart rate variability
4. Active psychosis or acute psychiatric crisis at time of enrolment
5. Inability to provide written informed consent
6. Pregnancy
7. Prior participation in this study under a different horse pairing

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Adults with PTSD Undergoing Ketamine-Assisted Therapy; Adults aged 19 years or older with a confirmed PTSD diagnosis (CAPS-5 score 23 or higher) who have independently arranged a ketamine-assisted therapy session with a licensed British Columbia physician or nurse practitioner. Participants wear a continuous wrist-worn biosensor (EmbracePlus) across preparation, intra-sessional, and integration monitoring phases. No intervention is administered by the researcher.

Device: Continuous wearable physiological monitoring (EmbracePlus, Empatica); Participants wear the EmbracePlus wrist-worn biosensor (Empatica Inc.) continuously throughout all study phases: a 3-7 day pre-session baseline period, the full duration of the KAT session, and 3-5 day monitoring windows at 1, 2, and 4 weeks post-session. The device records the interbeat interval stream, electrodermal activity (phasic and tonic components), skin temperature, and accelerometry. Both the HRV and EDA channels are required for valid arc-detection output. Data is streamed via Bluetooth to a secured local device and transferred to the study data layer within 24 hours of each monitoring session. Sessions with confirmed EDA channel loss exceeding 15% of the intra-sessional recording window are flagged and excluded from primary analysis.; Drug: Ketamine-assisted therapy (independently arranged); Participants independently arrange their own ketamine-assisted therapy sessions with a licensed physician or nurse practitioner in British Columbia or Alberta prior to enrolment. Ketamine is administered solely by the licensed treating provider under existing clinical frameworks. The researcher does not administer, possess, or dispense ketamine in connection with this study and has no clinical role during the session. All clinical decisions and participant safety oversight remain entirely with the treating provider. This exposure is observed, not researcher-administered.; Other: Structured pre- and post-session interviews; A structured pre-session interview (30-45 minutes) is conducted within 48 hours before the KAT session, audio-recorded with participant consent, focusing on self-narrative and subjective state rather than trauma content. A structured post-session interview (30-45 minutes) is conducted within 4 hours of session end, mapping subjective experience to the session timeline and administering the Post-Session Subjective Integration Scale. Trauma-informed communication is used throughout. Interviews are conducted by the PI or Co-Investigator only; the right to pause or end the interview at any time is explicitly communicated to participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-Sessional Autonomic Arc Trajectory Characterisation	Characterisation of the arc-position score trajectory generated by the JungleCODE algorithm applied to continuous HRV interbeat interval stream and electrodermal activity data from the EmbracePlus wearable. Arc position is expressed as the JungleCODE Arc-Position Score (range 0-100), where lower scores indicate greater sympathetic activation and maximal prior precision (aporia) and higher scores indicate greater parasympathetic dominance and regulatory restoration (ataraxia); higher scores represent a better autonomic outcome. Parameters include arc depth, inflection timing, transition event identification, and trajectory classification (progressive, regressive, plateau, or oscillating). The primary question is whether a coherent, characterisable autonomic arc can be detected within a ketamine-assisted therapy session.	During KAT session (up to 6 hours)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Between-dyad variability in pulse event frequency	Intraclass correlation coefficient (ICC, two-way mixed model, absolute agreement) to quantify how much of the variance in the frequency of confirmed simultaneous HRV coherence spikes at rater-marked windows is attributable to the specific horse-human pairing versus session-level or individual-level factors. This outcome addresses whether certain horse-human pairs are systematically more likely to produce detectable pulse events - a finding that would have implications for both therapeutic practice and the design of subsequent studies.	Through study completion, up to 12 months
Temporal Correspondence of Arc-Position Events to KAT Session Phases	Mapping of arc-position transition events onto recorded session phase timestamps (preparation, dosing onset, peak, integration onset) to characterise the temporal relationship between autonomic arc trajectory and the structured phases of the ketamine-assisted therapy session.	During KAT session (approximately 2 to 6 hours)
PCL-5 Score Change from Baseline	PTSD symptom severity as measured by the PTSD Checklist for DSM-5 (PCL-5 the Post-traumatic stress disorder of DSM-5 Checklist; range 0-80), where higher scores indicate greater PTSD symptom severity (worse outcome). Collected as an exploratory measure only. This pilot study is not powered to detect symptom-level change and no inferential analysis is pre-specified for this outcome.	Baseline, 2 weeks post-session, and 4 weeks post-session

Collaborators and Investigators

• Sponsor: Adriaan Dirk van der Wart

Publications and helpful links

General Publications

• Blevins CA, Weathers FW, Davis MT, Witte TK, Domino JL. The Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5): Development and Initial Psychometric Evaluation. J Trauma Stress. 2015 Dec;28(6):489-98. doi: 10.1002/jts.22059. Epub 2015 Nov 25.
• Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi.ajp.2013.13030392.
• Feder A, Costi S, Rutter SB, Collins AB, Govindarajulu U, Jha MK, Horn SR, Kautz M, Corniquel M, Collins KA, Bevilacqua L, Glasgow AM, Brallier J, Pietrzak RH, Murrough JW, Charney DS. A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. Am J Psychiatry. 2021 Feb 1;178(2):193-202. doi: 10.1176/appi.ajp.2020.20050596. Epub 2021 Jan 5.
• Carhart-Harris RL, Friston KJ. REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics. Pharmacol Rev. 2019 Jul;71(3):316-344. doi: 10.1124/pr.118.017160.
• Bonnelle V, Feilding A, Rosas FE, Nutt DJ, Carhart-Harris RL, Timmermann C. Autonomic nervous system activity correlates with peak experiences induced by DMT and predicts increases in well-being. J Psychopharmacol. 2024 Oct;38(10):887-896. doi: 10.1177/02698811241276788. Epub 2024 Sep 20.

Helpful Links

• Monitoring device
• Elegibility screening
• Secondary outcome measurement

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Autonomic Nervous System; Neuroplasticity; Heart Rate Variability; Electrodermal Activity; Wearable Biosensor; Physiological Synchrony; Ketamine-Assisted Therapy; Signal Characterization
• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: OMS-KAT-001 v1.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared. All data is held under the Open Medicine Studio sovereign data architecture in compliance with BC PIPA and PIPEDA. Data is stored in a self-managed encrypted database under physician-held encryption keys in Canadian jurisdiction (AWS ca-central-1). Anonymised arc-position trajectory data may be made available to academic research partners in future under a formal Data Use Agreement, as specified in participant consent documentation. No identifiable individual participant data will be shared under any circumstances.

Study Data/Documents

1. Study Protocol

Drug and device information, study documents

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