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

Official title

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

Overview

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.

Interventions

• 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.
• 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.
• 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.

Primary outcome measures

• Change from baseline in ADAS-Cog13 score at Month 6 [Time frame: Baseline, Month 6]

Secondary outcome measures (7)

• Change from baseline in ADAS-Cog13 score at Month 12 (OLE) [Time frame: Baseline, Month 6, Month 12 (OLE)]
• Change from baseline in ADCS-ADL score at Month 6 and Month 12 (OLE) [Time frame: Baseline, Month 6, Month 12 (OLE)]
• Change from baseline in PSQI score at Month 6 and Month 12 (OLE) [Time frame: Baseline, Month 6, Month 12 (OLE)]
• Change from baseline in NPI score at Month 6 and Month 12 (OLE) [Time frame: Baseline, Month 6, Month 12 (OLE)]
• Change from baseline in brain volume and hippocampal volume at Month 6 and Month 12 (OLE) [Time frame: Baseline, Month 6, Month 12 (OLE)]
• Change from baseline in SCD-Q9 score at Month 6 and Month 12 (OLE) [Time frame: Baseline, Month 6, Month 12 (OLE)]
• Change from baseline in CDR-SB score at Month 6 and Month 12 (OLE) [Time frame: Baseline, Month 6, Month 12 (OLE)]

Eligibility criteria

Inclusion criteria

• Age ≥50 and ≤85 years.
• 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.
• 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).

• Clinical Dementia Rating (CDR) global score of 0.5 (for MCI due to AD) or 1.0 (for mild AD dementia).
• If receiving acetylcholinesterase inhibitor (AChEI) and/or memantine therapy, the dose must have been stable for at least 3 months prior to screening.
• 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.
• The participant or their legally authorized representative is able and willing to provide written informed consent.

Exclusion criteria

• 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).
• Diagnosis of acute cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, myocardial infarction, or heart failure within the 3 months prior to screening.
• 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.
• 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 \[systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg\].
• Currently receiving medications that may interfere with study outcomes.
• Known hypersensitivity to the investigational drug or any of its excipients.
• Formal education of 1 year or less.
• Known history of severe organic disease or an anticipated survival of less than 12 months.
• Pregnant or breastfeeding women, or women of childbearing potential who refuse to use contraceptive measures.
• Participation in another clinical study within 30 days prior to screening, or currently enrolled in another clinical study.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07591727 · KY2026-015

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗