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

NCT07236190 | Recruiting Phase 1 FDA Drug

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

Brief Summary

The goal of this early phase, open-label, single arm clinical trial is to determine the 6-month effects and tolerability of NPC1 (parthenolide and ipriflavone) on biomarkers of Alzheimer's Disease among adults with objective indicators of seeding AD pathology that also have subjective cognitive concerns, Mild Cognitive Impairment, or Alzheimer's Disease (AD)

Conditions

Alzheimer Disease; Mild Cognitive Impairment (MCI); Subjective Cognitive Complaints (SCCs)

Keywords

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

Outcome Measures

Primary Outcomes (6)

• Effects on plasma p-tau217

  Changes from baseline intraindividual controlled condition

  6 months

• Effect on plasma GFAP

  Intraindividual changes from baseline

  6 months

• Effect on Neurofilament Light Chain (NfL)

  Intraindividual changes from baseline

  6 months

• Safety and Tolerability of NPC1

  Safety labs results including CBC, CMT, PT/INR tests

  Baseline through 6 months

• Effect on plasma abeta42/40

  Intraindividual changes from baseline

  6 months

• Safety and Tolerability of NPC1

  Assessment of Adverse Events Related to NPC1 Treatment

  Baseline through 6 months

Secondary Outcomes (1)

• Effects on plasma hsTNFalpha

  6 months

Other Outcomes (2)

• Exploratory effects on cognitive and functional measures

  6 months

• Exploratory intraindividual effects on CDR-SOB

  6 months

Study Arms (2)

Open label intervention with NPC1

ACTIVE COMPARATOR

Three capsules of NPC1 taken daily. One 300 mg cap of Ipriflavone and 1 cap of 2.5 mg Parthenolide in the morning; One 300 mg cap of Ipriflavone taken in the evening.

Drug: NPC1

Lead-in observational period

PLACEBO COMPARATOR

Serial blood draws to characterize pre-treatment biomarker status

Drug: NPC1-Placebo/Control

Interventions

NPC1 DRUG

NPC1 (parthenolide and ipriflavone)

Open label intervention with NPC1

NPC1-Placebo/Control DRUG

Participants with undergo serial blood draws off active drug

Also known as: Observational period

Lead-in observational 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:
• AD disease modifying monoclonal antibody treatment e.g., aducanumab or lecanemab
• 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

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

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

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 L. Bowman, ND, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Analytical chemists running the biomarker analyses are blind to whether participants were on active treatment of in the lead in phase of the trial
• 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 to intervention with blood biomarkers collected before and after treatment with two over the counter natural products combined as natural product combination-1 (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: April 17, 2026

Record last verified: 2026-04

Locations

US (1)