Biomarker-based Trial of NPC-1 for Alzheimer's Pathology (NPC1-AD)

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

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

Study Overview

• Status: Recruiting
• Conditions: Mild Cognitive Impairment (MCI); Alzheimer Disease; Subjective Cognitive Decline (SCD)
• Intervention / Treatment: Combination product: natural product combination-1 (NPC1)

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gene Bowman, N.D., M.P.H.; Phone Number: 857-282-5197; Email: glbowman@mgh.harvard.edu
• Study Contact Backup: Name: Brianna Wang; Phone Number: 857-282-1520; Email: bwang34@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Gene L. Bowman, ND, MPH; Phone Number: 857-282-5197; Email: glbowman@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 55 and older, male and female;
2. Subjective Cognitive Impairment or MCI or AD dementia per NIA-AA 2011 criteria;
3. Clinical Dementia Rating < or = to 2 and Mini Mental Status Exam > or = to 16;
4. Modified Hachinski Ischemic Score < or = to 4
5. Geriatric Depression Scale - 15 < 6 documenting absence from significant depressive syndromes
6. 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 ;
7. 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.
8. Sufficient vision and hearing to complete all tests
9. 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
10. General health status that will not interfere with the ability to complete the prospective study (these conditions are listed below in the study exclusion list)

Exclusion Criteria:

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

13. 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)
    • c. CNS active meds that have not been on stable doses for at least 2 months e.g., cimetidine, beta-blockers, and SSRIs
    • d. Neuroleptics, antiparkinsonian agents, systemic corticosteroids, and narcotic analgesics; in the case where these were used for a self-limited time they must have been discounted for a period of five half-lives prior to baseline visit
    • e. Over the counter supplements are not by themselves exclusionary, however, participants are asked not to change the dosing regimen over the course of the trial unless medically indicated; the presence and dose of these product are recorded
14. Participation in any Alzheimer's Disease interventional trial. Participation in other non-AD related trials will be evaluated at the discretion of the investigator
15. Currently pregnant. Positive pregnancy tests during the course of the trial will be evaluated at the discretion of the investigator.

Women of Child Bearing Potential (WOCBP)

For the purposes of this study, women of childbearing potential are defined as all women who are capable of becoming pregnant, unless they meet one of the following criteria:

1. 12-months post-menopausal
2. Post-hysterectomy/surgically sterile

If a female Participant does not meet either of these criteria they will be considered of childbearing potential and will have a serum pregnancy test performed at Screening, Visit 3 (2 months), Visit 6 (5 months), and Visit 10 (8 months).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Lead-in observational period; Serial blood-based biomarker collection
Active Comparator: Active interventional period; Serial post treatment blood-based biomarkers	Combination product: natural product combination-1 (NPC1); parthenolide plus ipriflavone; Other Names: parthenolide; ipriflavone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of NPC1	Assessment of Adverse Events Related to NPC1 Treatment	Baseline through 6 months
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma hsTNFalpha	intra-individual changes	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Dementia Rating sum of boxes		6 months
Montreal Cognitive Assessment		6 months
Safety and Tolerability	CBC w diff	Baseline through 6 months
Safety and Tolerability	CMP	Baseline through 6 months
Safety and Tolerability	PT/INR	Baseline through 6 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Gene Bowman, ND, MPH, Harvard/Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: October 28, 2025
• First Submitted That Met QC Criteria: November 15, 2025
• First Posted (Actual): November 19, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Intervention; Dietary Supplements; Mild Cognitive Impairment (MCI); Open Label; early phase clinical trial; blood based biomarkers
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; parthenolide; ipriflavone
• Other Study ID Numbers: 2025P000523

Drug and device information, study documents

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