A Study of the Metabolic Reconstruction Oral Biologics (Gut-X-001) Medication in People With Alzheimer's Disease (ESCAPE-AD) (ESCAPE-AD)

Efficacy, Safety, and Feasibility of Metabolic ReConstruction Oral Biologics (Gut-X-001) in Patients With Alzheimer's Disease: An Exploratory Clinical Trial （ESCAPE-AD）

This is an exploratory clinical trial aimed at preliminarily evaluating the efficacy, safety, and feasibility of orally administered Gut-X-001 in patients with Alzheimer's disease (AD). An open-label extension (OLE) study will also be conducted to further investigate the effects of Gut-X-001. The study will assess the effects of Gut-X-001 on cognitive function, activities of daily living, neuroimaging indicators, and AD-related plasma biomarkers in AD patients. Safety will be systematically monitored, including the incidence of adverse events and changes in hematological and organ function parameters. Furthermore, the study will explore the regulatory effects of Gut-X-001 versus placebo on venous blood redox-related indicators and gut microbiota metabolite levels at different time points, providing a basis for multi-target intervention strategies and offering systematic evidence for the scientific rationale, feasibility, and safety of Gut-X-001 in the clinical management of AD.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer s Disease
• Intervention / Treatment: Drug: Gut-X-001 + Placebo capsule; Drug: Gut-X-001; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yilong Wang; Phone Number: 13911666571; Email: Yilong528@aliyun.com
• Study Contact Backup: Name: Ling Guan; Phone Number: 13911076702; Email: lguanm@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. Age ≥50 and ≤85 years.
2. Diagnosis of Alzheimer's disease confirmed by a qualified neurologist based on the 2024 National Institute on Aging - Alzheimer's Association (NIA-AA) diagnostic criteria, with at least one abnormal core biomarker, including amyloid PET, CSF Aβ42/40, phosphorylated tau181 (p-tau181)/Aβ42, total tau (t-tau)/Aβ42, or plasma p-tau217.

3. MMSE score meeting the following criteria:

   If years of education ≤6: MMSE score between 16 and 24 (inclusive); If years of education >6: MMSE score between 18 and 27 (inclusive).

4. Clinical Dementia Rating (CDR) global score of 0.5 (for MCI due to AD) or 1.0 (for mild AD dementia).
5. If receiving acetylcholinesterase inhibitor (AChEI) and/or memantine therapy, the dose must have been stable for at least 3 months prior to screening.
6. Participants must have a reliable caregiver who has frequent contact with the participant (at least 4 days per week and at least 2 hours per day). The caregiver must accompany the participant to all study visits, provide meaningful input for scale assessments through sufficient interaction with the participant, and remain consistent throughout the study period wherever possible.
7. The participant or their legally authorized representative is able and willing to provide written informed consent.

Exclusion Criteria

1. Presence of other conditions that may contribute to cognitive impairment, including neurological disorders (e.g., vascular cognitive impairment, Parkinson's disease, frontotemporal dementia, Lewy body dementia) or psychiatric and affective disorders (e.g., severe anxiety/depression, schizophrenia).
2. Diagnosis of acute cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, myocardial infarction, or heart failure within the 3 months prior to screening.
3. Presence of other active or significant neurological conditions, including recurrent epileptic seizures, intracranial space-occupying tumors, vascular malformations (including arteriovenous malformations, arterial malformations, or cavernous malformations), or untreated aneurysms with a diameter >3 mm.
4. Severe hepatic impairment [ALT or AST >3× upper limit of normal (ULN), or concurrent acute hepatitis, chronic active hepatitis, or liver cirrhosis], renal impairment [estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m²], active malignancy, severe anemia, chronic obstructive pulmonary disease (COPD), immune system disorders, uncontrolled diabetes, or uncontrolled hypertension [systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg].
5. Currently receiving medications that may interfere with study outcomes.
6. Known hypersensitivity to the investigational drug or any of its excipients.
7. Formal education of 1 year or less.
8. Known history of severe organic disease or an anticipated survival of less than 12 months.
9. Pregnant or breastfeeding women, or women of childbearing potential who refuse to use contraceptive measures.
10. Participation in another clinical study within 30 days prior to screening, or currently enrolled in another clinical study.
11. Any other condition that, in the investigator's judgment, makes the participant unsuitable for enrollment or unable to complete the study procedures and follow-up visits, such as psychiatric illness or physical conditions that preclude compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control Group; Placebo	Drug: Placebo; Participants will receive 4 placebo capsules (0 mg of active ingredient per capsule) orally per administration, 3 times daily (at 8:00 AM, 12:00 PM, and 10:00 PM), administered before meals and before bedtime. Placebo capsules are identical in appearance to the active Gut-X-001 capsules to maintain blinding.
Experimental: Low-Dose Group; Low-Dose Gut-X-001	Drug: Gut-X-001 + Placebo capsule; Participants will receive Gut-X-001 orally at a dose of 2 active capsules (10 mg of active ingredient per capsule) plus 2 placebo capsules (0 mg of active ingredient per capsule) per administration, 3 times daily (at 8:00 AM, 12:00 PM, and 10:00 PM), administered before meals and before bedtime. Total active ingredient per administration: 20 mg; total daily dose: 60 mg.
Experimental: High-Dose Group; High-Dose Gut-X-001	Drug: Gut-X-001; Participants will receive Gut-X-001 orally at a dose of 4 active capsules (10 mg of active ingredient per capsule) per administration, 3 times daily (at 8:00 AM, 12:00 PM, and 10:00 PM), administered before meals and before bedtime. Total active ingredient per administration: 40 mg; total daily dose: 120 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in ADAS-Cog13 score at Month 6	Change from baseline in the Alzheimer's Disease Assessment Scale - Cognitive Subscale 13-item version (ADAS-Cog13) score. Higher scores indicate greater cognitive impairment.	Baseline, Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in ADAS-Cog13 score at Month 12 (OLE)	Change from baseline and from Month 6 in ADAS-Cog13 score during the open-label extension (OLE) phase. Higher scores indicate greater cognitive impairment.	Baseline, Month 6, Month 12 (OLE)
Change from baseline in ADCS-ADL score at Month 6 and Month 12 (OLE)	Change from baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale score. Lower scores indicate greater functional impairment.	Baseline, Month 6, Month 12 (OLE)
Change from baseline in PSQI score at Month 6 and Month 12 (OLE)	Change from baseline in the Pittsburgh Sleep Quality Index (PSQI) score. Higher scores indicate poorer sleep quality.	Baseline, Month 6, Month 12 (OLE)
Change from baseline in NPI score at Month 6 and Month 12 (OLE)	Change from baseline in the Neuropsychiatric Inventory (NPI) score. Higher scores indicate more severe neuropsychiatric symptoms.	Baseline, Month 6, Month 12 (OLE)
Change from baseline in brain volume and hippocampal volume at Month 6 and Month 12 (OLE)	Change from baseline in brain volume and hippocampal volume as measured by structural neuroimaging (MRI).	Baseline, Month 6, Month 12 (OLE)
Change from baseline in SCD-Q9 score at Month 6 and Month 12 (OLE)	Change from baseline in the Subjective Cognitive Decline Questionnaire 9-item version (SCD-Q9) score.	Baseline, Month 6, Month 12 (OLE)
Change from baseline in CDR-SB score at Month 6 and Month 12 (OLE)	Change from baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) score. Higher scores indicate greater disease severity.	Baseline, Month 6, Month 12 (OLE)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of ≥90% medication adherence at Month 6	Proportion of participants who complete at least 90% of the prescribed dosing regimen during the double-blind phase.	Month 6
Incidence of clinically significant abnormal CBC findings at Day 7, Month 3, Month 6, and Month 12 (OLE)	Proportion of participants meeting any of the following criteria: (i) anemia (hemoglobin <90 g/L in males or <85 g/L in females, or requiring transfusion); (ii) thrombocytopenia (platelets <50.0×10⁹/L or requiring transfusion); (iii) leukopenia (WBC <1.5×10⁹/L, lymphocytes <0.5×10⁹/L, or neutrophils <0.60×10⁹/L); or (iv) any CBC abnormality deemed clinically significant by the investigator.	Day 7, Month 3, Month 6, Month 12 (OLE)
Incidence of clinically significant hepatic biochemical abnormalities at Day 7, Month 3, Month 6, and Month 12 (OLE)	Proportion of participants meeting any of the following criteria: (i) ALT or AST >5× ULN; (ii) ALT or AST >3× ULN with total bilirubin >2× ULN (Hy's Law); or (iii) ALT or AST >3× ULN with symptoms of hepatic injury (e.g., nausea, vomiting, jaundice).	Day 7, Month 3, Month 6, Month 12 (OLE)
Incidence of acute kidney injury or significant renal function deterioration at Day 7, Month 3, Month 6, and Month 12 (OLE)	Proportion of participants meeting any of the following criteria: (i) acute: serum creatinine increase ≥1.5-fold from baseline (confirmed or presumed to have occurred within 7 days) or increase ≥26.5 µmol/L (0.3 mg/dL) within 48 hours; or (ii) chronic: eGFR decrease ≥30% from baseline.	Day 7, Month 3, Month 6, Month 12 (OLE)
Incidence of body weight increase >10% from baseline at Day 7, Month 3, Month 6, and Month 12 (OLE)	Proportion of participants with a body weight increase of more than 10% compared to baseline.	Day 7, Month 3, Month 6, Month 12 (OLE)
Incidence of binge eating episodes at Day 7, Month 3, Month 6, and Month 12 (OLE)	Proportion of participants experiencing binge eating, defined as eating an unusually large amount of food within a discrete period (e.g., 2 hours) accompanied by a sense of loss of control over eating behavior.	Day 7, Month 3, Month 6, Month 12 (OLE)
Incidence of adverse events and serious adverse events at Day 7, Month 3, Month 6, and Month 12 (OLE)	Proportion of participants experiencing any adverse event (AE) or serious adverse event (SAE) during the study period.	Day 7, Month 3, Month 6, Month 12 (OLE)
Incidence of drug-related adverse events and serious adverse events at Day 7, Month 3, Month 6, and Month 12 (OLE)	Proportion of participants experiencing AEs or SAEs assessed by the investigator as related to the study drug.	Day 7, Month 3, Month 6, Month 12 (OLE)
Rate of treatment discontinuation due to adverse events or serious adverse events at Day 7, Month 3, Month 6, and Month 12 (OLE)	Proportion of participants who discontinue study treatment due to AEs or SAEs.	Day 7, Month 3, Month 6, Month 12 (OLE)
Change from baseline in venous blood H₂O₂ concentration and oxidative stress-related indicators at Month 6 and Month 12 (OLE)	Change from baseline in venous blood hydrogen peroxide (H₂O₂) concentration and other oxidative stress-related indicators.	Baseline, Month 6, Month 12 (OLE)
Change from baseline in Aβ and tau protein deposition assessed by PET-CT at Month 6 and Month 12 (OLE)	Change from baseline in amyloid-β (Aβ) and tau protein deposition as assessed by PET-CT imaging.	Baseline, Month 6, Month 12 (OLE)
Change from baseline in AD-related plasma biomarker levels at Month 6 and Month 12 (OLE)	Change from baseline in plasma biomarker levels including p-Tau217, NfL, NELL1, ENO2, ST2, LIFR, CD33, CHI3L1, PPY, FAM3B, and other relevant markers.	Baseline, Month 6, Month 12 (OLE)
Change from baseline in gut microbiota metabolite levels at Month 6 and Month 12 (OLE)	Change from baseline in gut microbiota metabolite-related indicators.	Baseline, Month 6, Month 12 (OLE)

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: KY2026-015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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