SCF-ECCA-AE-FIH-CTD-0004
First-in-Human (FIH) Clinical Trial Design
Autoimmune Encephalopathy
Adaptive Biomarker-Guided Precision Acupuncture Clinical Administration Protocol
SCF Multi-Omics Neuroimmune Connectomic Reconstruction Platform
Encephalopathy Connectomic Collapse Atlas (ECCA-AE)
I. TRIAL OVERVIEW
Study Title
A First-in-Human Adaptive Biomarker-Guided Precision Acupuncture Study for Autoimmune Encephalopathy Utilizing the SCF Encephalopathy Connectomic Collapse Atlas (ECCA-AE).
Study Phase
Phase 0/Ia
Trial Design
- Prospective
- Adaptive
- Biomarker-guided
- Open-label
- Safety-first dose-escalation neuromodulation protocol
- Real-time neuroimmune-connectomic monitoring
- Integrated biomarker-response guided administration
Study Duration
Total Duration
20 Weeks
Screening
4 Weeks
Active Treatment
12 Weeks
Follow-Up
4 Weeks
II. PRIMARY OBJECTIVES
Safety
Evaluate:
- Serious adverse events
- Autoimmune flare activation
- Neurological deterioration
- New seizures
- Autonomic instability
- Cognitive worsening
- New MRI lesion development
- Psychiatric decompensation
Feasibility
Evaluate:
- Treatment adherence
- Biomarker monitoring compliance
- Neuroimaging feasibility
- Continuous autonomic monitoring compliance
- Acupuncture tolerability
III. SECONDARY OBJECTIVES
Evaluate:
- Neuroimmune stabilization
- Autoantibody reduction trends
- Connectomic restoration
- Cognitive improvement
- Autonomic recovery
- Neuroaxonal injury reduction
- Quality-of-life improvement
- Reduction in relapse frequency
IV. TARGET POPULATION
Eligible Autoimmune Encephalopathy Subtypes
Autoimmune Encephalitis
- Anti-NMDA Receptor
- LGI1
- CASPR2
- GABA-B
- AMPAR
- DPPX
Systemic Autoimmune Neuroinflammatory Disease
- Lupus-associated encephalopathy
- Sjögren encephalopathy
- Hashimoto encephalopathy
- Seronegative autoimmune encephalopathy
Chronic Relapsing Autoimmune Encephalopathy
Stable disease only
V. INCLUSION CRITERIA
Criterion | Requirement |
Age | 18–80 |
Confirmed autoimmune encephalopathy | Yes |
Autoantibody positive or clinically confirmed | Yes |
MoCA | 12–28 |
Stable immunotherapy | ≥30 days |
MRI stable | ≤90 days |
No acute relapse | ≥30 days |
SCF Autoimmune Connectomic Score | 20–80 |
VI. EXCLUSION CRITERIA
- Active encephalitis relapse
- ICU-level illness
- Status epilepticus
- Progressive malignancy
- Active CNS infection
- Severe psychosis
- Mechanical ventilation
- Pregnancy
- Hemodynamic instability
- New immunotherapy initiation <30 days
VII. REAL-TIME SCF BIOMARKER PANEL
Tier 1 Autoantibody Activity Panel
Biomarker | Assay | Frequency |
NMDAR IgG | Cell-Based Assay | Every 2 Weeks |
LGI1 IgG | Cell-Based Assay | Every 2 Weeks |
CASPR2 IgG | Cell-Based Assay | Every 2 Weeks |
GABA-BR IgG | Cell-Based Assay | Every 2 Weeks |
AMPAR IgG | Cell-Based Assay | Every 2 Weeks |
ANA | Immunofluorescence | Monthly |
dsDNA | ELISA | Monthly |
Endpoint
Autoimmune Driver Activity Index (ADAI)
Tier 2 Neuroimmune Activation Panel
Biomarker | Assay | Frequency |
IL-6 | Multiplex | Weekly |
TNF-α | Multiplex | Weekly |
IL-1β | Multiplex | Weekly |
IFN-γ | Multiplex | Weekly |
CXCL13 | ELISA | Weekly |
Endpoint
Neuroimmune Amplification Index (NAI)
Tier 3 Neuroaxonal Injury Panel
Biomarker | Assay | Frequency |
NfL | Simoa | Weekly |
Total Tau | Simoa | Every 2 Weeks |
UCH-L1 | ELISA | Weekly |
NSE | CLIA | Weekly |
Endpoint
Neuroaxonal Injury Index (NAII)
Tier 4 Neuroglial Activation Panel
Biomarker | Assay | Frequency |
GFAP | Simoa | Weekly |
YKL-40 | ELISA | Weekly |
sTREM2 | ELISA | Every 2 Weeks |
S100B | Immunoassay | Weekly |
Endpoint
Glial Activation Severity Score (GASS)
Tier 5 BBB Integrity Panel
Biomarker | Assay | Frequency |
Albumin Quotient | CSF/Serum | Baseline / Week 12 |
MMP-9 | ELISA | Weekly |
VEGF | ELISA | Every 2 Weeks |
S100B | Immunoassay | Weekly |
Endpoint
BBB Permeability Index (BBPI)
Tier 6 Connectomic Monitoring Panel
Biomarker | Assay | Frequency |
qEEG Connectivity | Weekly | |
EEG Delta Power | Weekly | |
EEG Theta Excess | Weekly | |
rs-fMRI Connectivity | Baseline / Week 12 | |
DTI Fractional Anisotropy | Baseline / Week 12 |
Endpoint
Connectomic Collapse Index (CCI)
Tier 7 Autonomic Monitoring Panel
Biomarker | Assay | Frequency |
HRV SDNN | Daily | |
RMSSD | Daily | |
LF/HF Ratio | Daily | |
COMPASS-31 | Weekly | |
Orthostatic Test | Weekly |
Endpoint
Autonomic Collapse Index (ACI)
VIII. ACUPUNCTURE ADMINISTRATION PROTOCOL
Cohort A
Low Intensity
Frequency:
2 Sessions Weekly
Duration:
20 Minutes
Primary Points:
- GV20
- ST36
- PC6
- HT7
- LI11
Goal:
Neuroimmune stabilization
Cohort B
Moderate Intensity
Frequency:
3 Sessions Weekly
Duration:
30 Minutes
Additional Points:
- GV24
- LI4
- SP6
- LV3
- CV17
Goal:
Connectomic restoration
Cohort C
High Intensity
Frequency:
5 Sessions Weekly
Duration:
40 Minutes
Additional Points:
- Sishencong
- Yintang
- KI3
- Auricular Shenmen
- GB20
Goal:
Maximum connectomic and autonomic restoration
IX. REAL-TIME ESCALATION RULES
Escalation requires ALL criteria maintained for 14 days
Autoimmune Activity
Autoantibody titer reduction
≥15%
OR stable low-positive status
Neuroimmune Activity
IL-6 reduction
≥20%
AND
TNF-α reduction
≥15%
Neuroaxonal Injury
NfL stable or reduced
Connectomics
qEEG connectivity improvement
≥10%
Cognition
MoCA improvement
≥2 points
Autonomics
HRV SDNN improvement
≥10%
Escalation Action
Advance one cohort level
within 7 days
X. DE-ESCALATION RULES
Immediate de-escalation if ANY occur
Autoimmune Reactivation
Autoantibody titer increase
≥25%
Neuroimmune Flare
IL-6 increase
≥50%
OR
CXCL13 increase
≥30%
Neuroaxonal Injury
NfL increase
≥25%
Glial Injury
GFAP increase
≥25%
Connectomics
qEEG deterioration
≥20%
Cognition
MoCA decline
≥3 points
Clinical Events
- New seizure
- New psychosis
- Relapse symptoms
- New focal neurologic deficit
Action
Return to previous cohort
Repeat monitoring
within 24–48 hours
XI. STOPPING RULES
Immediate study suspension if:
- Status epilepticus
- ICU admission
- Acute encephalitis relapse
- New MRI inflammatory lesion
- Severe psychosis
- Unexpected SAE
Subject Withdrawal
If:
- NfL doubles from baseline
- GFAP doubles from baseline
- Autoantibody titers double
- SCF Autoimmune Connectomic Score worsens >30%
XII. PRIMARY ENDPOINTS
Safety Endpoints
- SAE incidence
- Relapse rate
- Seizure occurrence
- Cognitive deterioration
- Psychiatric deterioration
Biomarker Safety Endpoints
- NfL stability
- GFAP stability
- Cytokine stability
- Autoantibody stability
XIII. SECONDARY ENDPOINTS
Connectomic Restoration
- qEEG connectivity
- rs-fMRI connectivity
- DTI FA
Cognitive Recovery
- MoCA
- Trail Making Test-B
- Digit Symbol Substitution
Autonomic Recovery
- HRV
- COMPASS-31
Autoimmune Stabilization
- Autoantibody titers
- CXCL13
- IL-6
- TNF-α
Quality of Life
- EQ-5D-5L
- Neuro-QoL
- PROMIS Cognitive Function
XIV. COMPOSITE SCF AUTOIMMUNE RESPONSE SCORE (SCF-AERS)
Domain | Weight |
Autoantibody Activity | 20% |
Neuroimmune Activity | 20% |
Neuroaxonal Injury | 15% |
Glial Activation | 15% |
BBB Integrity | 10% |
Connectomics | 10% |
Autonomics | 5% |
Cognition | 5% |
Interpretation
Score Change | Response |
>30% Improvement | Major Response |
15–30% Improvement | Moderate Response |
5–15% Improvement | Minor Response |
±5% | Stable |
>10% Worsening | Progression |
XV. FDA-ALIGNED REAL-TIME SAFETY DASHBOARD
Green Zone
- Autoantibody stable/decreasing
- NfL stable
- GFAP stable
- HRV improving
- qEEG improving
Action:
Continue protocol
Yellow Zone
- Mild cytokine increase
- Mild HRV decline
- Small qEEG deterioration
Action:
Increase monitoring frequency
No escalation
Red Zone
- Autoantibody increase ≥25%
- NfL increase ≥25%
- GFAP increase ≥25%
- New seizure
- New psychosis
- MoCA decline ≥3
Action:
Immediate de-escalation
Safety review
XVI. TRANSLATIONAL DECISION GATES
GO
Requirements:
- No SAE signal
- Autoantibody stabilization
- Improved qEEG connectivity
- Improved MoCA
- Stable NfL/GFAP
Proceed to Phase Ib
CONDITIONAL GO
Requirements:
- Acceptable safety
- Mixed biomarker response
- No relapse signal
Protocol refinement required
NO-GO
Requirements:
- Relapse activation
- Connectomic deterioration
- Biomarker worsening
- Safety concerns
Terminate development
NEXT CLINICAL ADMINISTRATION PROTOCOL
SCF-ECCA-SEP-FIH-CTD-0005
Septic Encephalopathy FIH Clinical Trial Design
MASTER REGISTRY INDEX
- SCF-ECCA-AE-FIH-CTD-0004 — Autoimmune Encephalopathy FIH Clinical Trial Design
- SCF-ECCA-AE-BIO-0004 — Autoimmune Encephalopathy Biomarker Panel
- SCF-ECCA-AE-ACU-0004 — Autoimmune Encephalopathy Acupuncture Point Mapping Atlas
- SCF-ECCA-0001 — Encephalopathy Connectomic Collapse Atlas
- SCF-CLINDEV-0001 — SCF Clinical Development Framework
- SCF-BIOMARKER-ENDPOINTS-0001 — SCF Biomarker Endpoint Validation Framework
- SCF-ACU-NEURO-ATLAS-0001 — SCF Neural Mapping Schema
- SCF-AUTOIMMUNE-CONNECTOME-0001 — Autoimmune Neuroimmune Connectomic Reconstruction Framework