Biomarker-based Trial of NPC-1 for Alzheimer's Pathology

NCT07236190 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 2025P000523
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This early phase, open label, single arm clinical trial will determine the intraindividual safety, tolerability and effects of NPC1 (parthenolide and ipriflavone) on blood-based biomarkers of Alzheimer's disease (AD) pathology among adults with subjective cognitive decline, mild cognitive impairment, or Alzheimer's disease and objective indicators of seeding AD pathology

Conditions

Alzheimer Disease; Mild Cognitive Impairment (MCI); Subjective Cognitive Decline (SCD)

Keywords

Open Label; Dietary Supplements; Alzheimer's Disease; Mild Cognitive Impairment (MCI); Intervention; early phase clinical trial; blood based biomarkers

Outcome Measures

Primary Outcomes (5)

• plasma p-tau217

  Intra-individual changes from pre-treatment observational period to post-treatment interventional period

  6 months

• plasma glial fibrillary acidic protein

  Intraindividual changes

  6 months

• plasma neurofilament light chain

  Intra-individual changes

  6 months

• plasma abeta42 / abeta40

  Intraindividual changes

  6 months

• Safety and Tolerability of NPC1

  Assessment of Adverse Events Related to NPC1 Treatment

  Baseline through 6 months

Secondary Outcomes (1)

• plasma hsTNFalpha

  6 months

Other Outcomes (5)

• Safety and Tolerability

  Baseline through 6 months

• Safety and Tolerability

  Baseline through 6 months

• Safety and Tolerability

  Baseline through 6 months

Study Arms (2)

Lead-in observational period

NO INTERVENTION

Serial blood-based biomarker collection

Active interventional period

ACTIVE COMPARATOR

Serial post treatment blood-based biomarkers

Combination Product: natural product combination-1 (NPC1)

Interventions

natural product combination-1 (NPC1) COMBINATION_PRODUCT

parthenolide plus ipriflavone

Also known as: parthenolide, ipriflavone

Active interventional period

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55 and older, male and female;
• Subjective Cognitive Impairment or MCI or AD dementia per NIA-AA 2011 criteria;
• Clinical Dementia Rating \< or = to 2 and Mini Mental Status Exam \> or = to 16;
• Modified Hachinski Ischemic Score \< or = to 4
• Geriatric Depression Scale - 15 \< 6 documenting absence from significant depressive syndromes
• Other medications including non-disease modifying for MCI and AD (e.g., acetylcholine esterase inhibitor, N-methyl D-aspartate receptor antagonist) stable \> or = to 3-months ;
• Biomarker evidence of AD pathology: Plasma abeta42/40 ratio \< or = to 0.12 AND Plasma p-tau217 \> or = to 0.25 OR Amyloid PET positive (centiloid \> or = to 20) as part of routine clinical care.
• Sufficient vision and hearing to complete all tests
• Study partner available with frequent (at least 1 hour/day or 1 day/week) contact with participant to provide collateral information about cognition, daily functioning, adverse events reporting, and support for study drug intake

You may not qualify if:

• CDR \> 2 MMSE \< 16;
• Significant CNS disease within the last 2 years (i.e., brain tumor, seizure disorder, subdural hematoma, cranial arteritis, cortical stroke);
• Alcohol or substance abuse according to DSM-IV criteria within the last 2 years
• Major depressive disorder or anxiety within the last year; Schizophrenia, bipolar disorder or other major psychiatric disorder defined by DSM-IV criteria
• Abnormal labs indicating potential reversible causes of dementing illness such as vitamin B12 deficiency, thyroid disease, or UTI (documented bacterial colonization is acceptable)
• Unstable or significantly symptomatic CVD (e.g. CAD with frequent angina, CHF with dyspnea at rest)
• Hypertension: defined as uncontrolled BP \> 160/100
• Clinical symptomatic orthostatic hypotension
• Diabetes mellitus that requires insulin injections
• Hachinski ischemic score \> or = to 4
• Cancer within the last 5 years, apart from localized prostate cancer (Gleason Grade \< 3) and non-metastatic skin cancers (melanoma).
• Illness that requires \>1 visit /month to a clinician
• Medications and dietary supplements:
• a. AD disease modifying monoclonal antibody treatment e.g., aducanumab or lecanemab
• b. Dietary supplements containing parthenolide or ipriflavone (1-month wash out period prior to enrollment is permitted)

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02129, United States

RECRUITING

Related Publications (1)

• Dodge HH, Chen L, Wu CY, Cutter G, Bowman GL, Feldman HH, Arnold SE. Seeking optimal repeated fluid biomarker assessments to enhance precision and statistical power in clinical trials: SLIM method. Alzheimers Dement. 2025 Oct;21(10):e70787. doi: 10.1002/alz.70787.

  PMID: 41122812 BACKGROUND

Related Links

• Harvard-MGH-McCance Center for Brain Health-Clinical Trials Platform

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

parthenolide; ipriflavone

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Study Officials

• Gene Bowman, ND, MPH

  Harvard/Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gene Bowman, N.D., M.P.H.

CONTACT

857-282-5197; glbowman@mgh.harvard.edu

Brianna Wang

CONTACT

857-282-1520; bwang34@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Analytical chemists running the biomarker analyses are blind to whether participants are in the lead in or active phase of the intervention
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Trials

Model Details: Single arm, lead-in with blood-based biomarkers collected before and after treatment with a natural product combination (NPC1)

Study Record Dates

• First Submitted: October 28, 2025
• First Posted: November 19, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: June 8, 2026

Record last verified: 2026-06

Locations

US (1)