SCF Multi-Omics Neuroimmune Connectomic Reconstruction Platform | Adaptive Biomarker-Guided Precision Acupuncture Clinical Administration Protocol — Septic Encephalopathy

SCF-ECCA-SEP-FIH-CTD-0005

First-in-Human Clinical Trial Design

Septic Encephalopathy

Adaptive Biomarker-Guided Precision Acupuncture Clinical Administration Protocol

I. Trial Overview

Study Title: First-in-Human Adaptive Biomarker-Guided Precision Acupuncture Study for Septic Encephalopathy Using the SCF Encephalopathy Connectomic Collapse Atlas.

Phase: Phase 0/Ia

Design: Prospective, ICU-compatible, safety-first, open-label, biomarker-guided feasibility trial.

Duration: 8 weeks total: screening/stabilization up to 72 hours, active treatment 14 days, recovery follow-up 6 weeks.

II. Target Population

Adults with sepsis-associated encephalopathy after initial stabilization.

Category	Requirement
Age	18–80
Diagnosis	Sepsis or septic shock with altered mentation
Neurologic status	CAM-ICU positive, GCS 9–15, or delirium phenotype
Hemodynamics	Stable or improving for ≥12–24 hours
Standard care	Antibiotics, source control, fluids, vasopressors/organ support as needed
SCF Septic Connectomic Score	20–80

III. Exclusion Criteria

Uncontrolled septic shock
GCS ≤8 without neurocritical clearance
Status epilepticus
Active CNS infection requiring separate protocol
Severe thrombocytopenia or unsafe bleeding risk
Uncontrolled coagulopathy
Mechanical ventilation instability
New stroke or intracranial hemorrhage
Unstable arrhythmia
Pregnancy

IV. Real-Time Biomarker Panel

Tier	Biomarker	Assay	Frequency
Sepsis Burden	Lactate, PCT, CRP, WBC, NLR	Chemistry/CBC/CLIA immunoassay	Daily ICU phase
Cytokine Storm	IL-6, TNF-α, IL-1β, IL-8	Multiplex	Every 48 h
Endothelial Injury	Ang-2, vWF, Syndecan-1, ICAM-1	ELISA/immunoassay	Twice weekly
Neuroglial Injury	GFAP, S100B, YKL-40	Simoa/immunoassay	Twice weekly
Neuroaxonal Injury	NfL, Tau, NSE, UCH-L1	Simoa/CLIA	Twice weekly
Bioenergetics	Lactate/pyruvate ratio, cf-mtDNA	Chemistry/LC-MS/qPCR	Twice weekly
Connectomics	qEEG delta/theta, qEEG connectivity	qEEG	2–3 times weekly
Autonomics	HRV SDNN, RMSSD, LF/HF	ECG/wearable	Continuous or daily
Cognition/Delirium	CAM-ICU, GCS, RASS	Clinical scale	Each shift

V. Acupuncture Administration Protocol

Cohort A — ICU Low-Intensity Stabilization

Parameter	Protocol
Frequency	2 sessions/week
Duration	10–15 minutes
Points	ST36, PC6, LI11, GV20, Yintang
Goal	Neuroimmune and autonomic stabilization

Cohort B — Moderate Recovery Phase

Parameter	Protocol
Frequency	3 sessions/week
Duration	20 minutes
Additional Points	LI4, CV17, HT7, ST25
Goal	Delirium, vagal, gut-barrier, and cytokine modulation

Cohort C — Post-ICU Neurorecovery

Parameter	Protocol
Frequency	3 sessions/week
Duration	30 minutes
Additional Points	Sishencong, SP6, KI3, GB20
Goal	Connectomic restoration and cognitive recovery

VI. Escalation Thresholds

Escalate only if all are met for 72 hours:

Domain	Escalation Requirement
Hemodynamics	No increasing vasopressor requirement
Lactate	Decrease ≥20% or <2 mmol/L
Neuroimmune	IL-6 decrease ≥20%
Neuroglial	GFAP stable or decreasing
Neuroaxonal	NfL stable or decreasing
Autonomics	HRV SDNN improves ≥10%
Connectomics	qEEG connectivity improves ≥10%
Clinical	CAM-ICU improves or GCS stable/improving

VII. De-Escalation Thresholds

Immediate de-escalation if any occur:

Domain	Threshold
Lactate	Increase ≥25% or >4 mmol/L with deterioration
Vasopressors	Increasing requirement
IL-6	Increase ≥50%
GFAP	Increase ≥25%
NfL	Increase ≥25%
qEEG	Connectivity deterioration ≥20%
Neurologic	New seizure, GCS drop ≥2 points
Cardiovascular	New unstable arrhythmia
Infection	New source-control failure or septic shock relapse

VIII. Stopping Rules

Stop subject participation for:

Septic shock recurrence requiring major escalation
Status epilepticus
New focal neurologic deficit
ICU deterioration attributed to intervention
NfL or GFAP doubling from baseline
SCF Septic Connectomic Score worsening >30%
Unexpected serious adverse event

IX. Primary Endpoints

Endpoint Class	Measures
Safety	SAE rate, hemodynamic instability, seizure occurrence, ICU deterioration
Feasibility	Completion rate, session tolerability, biomarker collection success
Biomarker Safety	Stable/decreasing GFAP, NfL, IL-6, lactate
ICU Neurologic Safety	CAM-ICU, GCS, RASS stability

X. Secondary Endpoints

Domain	Endpoint
Delirium	CAM-ICU conversion, delirium-free days
Connectomics	qEEG delta/theta reduction, improved connectivity
Autonomics	HRV SDNN/RMSSD improvement
Inflammation	IL-6, TNF-α, CRP reduction
Endothelial	Ang-2, vWF, Syndecan-1 stabilization
Functional Recovery	MoCA at follow-up, EQ-5D-5L, ICU-free days

XI. SCF Septic Encephalopathy Response Score

Domain	Weight
Sepsis Burden	20%
Cytokine Storm	20%
Endothelial Injury	15%
Neuroglial Injury	15%
Neuroaxonal Injury	10%
Connectomics	10%
Autonomics	5%
Cognition/Delirium	5%

Score Change	Response
>30% improvement	Major response
15–30% improvement	Moderate response
5–15% improvement	Minor response
±5%	Stable
>10% worsening	Progression

XII. Real-Time Safety Dashboard

Zone	Criteria	Action
Green	Lactate down, vasopressors stable/decreasing, GFAP/NfL stable, HRV/qEEG improving	Continue
Yellow	Mild cytokine rise, mild HRV decline, lactate fluctuation	Hold escalation, increase monitoring
Red	Lactate ↑ ≥25%, vasopressor escalation, GFAP/NfL ↑ ≥25%, seizure, GCS drop	De-escalate or withdraw

XIII. Translational Decision Gates

Go: no SAE signal, stable hemodynamics, improved delirium metrics, stable/decreasing GFAP/NfL, improved qEEG or HRV.

Conditional Go: acceptable safety with mixed biomarker response.

No-Go: worsening shock, biomarker injury signal, neurologic deterioration, or intervention intolerance.

MASTER REGISTRY INDEX

SCF-ECCA-SEP-FIH-CTD-0005 — Septic Encephalopathy FIH Clinical Trial Design
SCF-ECCA-SEP-BIO-0005 — Septic Encephalopathy Biomarker Panel
SCF-ECCA-SEP-ACU-0005 — Septic Encephalopathy Acupoint Neuro-Circuit Mapping Atlas
SCF-ECCA-0001 — Encephalopathy Connectomic Collapse Atlas
SCF-CLINDEV-0001 — SCF Clinical Development Framework