Alzheimer DiseasePhase 2NPC1-ADNCT07236190
Biomarker-based Trial of NPC-1 for Alzheimer's Pathology
A Phase 2 study testing natural product combination-1 (NPC1) in people with Alzheimer Disease and Mild Cognitive Impairment (MCI), run by Massachusetts General Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Alzheimer Disease, Mild Cognitive Impairment (MCI), Subjective Cognitive Decline (SCD)
- What is being tested?
- natural product combination-1 (NPC1)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2026to Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 55 and older, male and female;
- Subjective Cognitive Impairment or MCI or AD dementia per the Revised criteria for diagnosis and staging of Alzheimer's disease 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 1-month prior to screening visit;
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- Biomarker evidence of AD pathology: Plasma abeta42/40 ratio < or = to 0.12 AND Plasma p-tau217 > or = to 2.1 pg/mL 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
- 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)
Who cannot join
- CDR > 2 MMSE < 16;
- Other significant CNS disease within the last 2 years (i.e., brain tumor, seizure disorder, subdural hematoma, cranial arteritis, cortical stroke) That would impact the participant's ability to complete the study;
- 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) or INR > 1.2 (1.3 or higher) or platelets < 100 K/uL at screening
- Unstable or significantly symptomatic CVD (e.g. CAD with frequent angina, CHF with dyspnea at rest)
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- 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., donanemab (Kisunla) or lecanemab (Leqembi). Wash out period of five half-lives prior to screening visit is permitted e.g., > or = 60 days since last dose of donanemab and > or = 35 days since last dose of lecanemab)
- b. Dietary supplements containing parthenolide or ipriflavone (1-month wash out period prior to screening is permitted)
- c. CNS active meds that have not been on stable doses for at least 1 month prior to screening visit 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 discontinued for a period of five half-lives prior to screening 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
- f. Anticoagulation therapy: Vitamin K antagonist: warfarin (Coumadin, jantoven)
- Participation in any Alzheimer's Disease interventional trial. Participation in other non-AD related trials will be evaluated at the discretion of the investigator
- 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:
- 12-months post-menopausal
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02129
Brianna Wang, MS, 857-282-1520, npc1clinicaltrial@mgb.org
About this study
Official title: 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
- Being tested
- natural product combination-1 (NPC1)
- Keywords
- Open Label, Dietary Supplements, Alzheimer's Disease, Mild Cognitive Impairment (MCI), Intervention, early phase clinical trial, blood based biomarkers
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
natural product combination-1 (NPC1)Combination product
Also called parthenolide, ipriflavone
parthenolide plus ipriflavone
| Study group | Role | What they receive |
|---|---|---|
| Lead-in observational period | No intervention | Serial blood-based biomarker collection |
| Active interventional period | Active comparator | Serial post treatment blood-based biomarkers Receives: Combination Product: natural product combination-1 (NPC1) |
What is being measured
The primary outcome is the main question the study is designed to answer.
plasma p-tau217
Intra-individual changes from pre-treatment observational period to post-treatment interventional period
Measured: 6 months
plasma glial fibrillary acidic protein
Intraindividual changes
Measured: 6 months
plasma neurofilament light chain
Intra-individual changes
Measured: 6 months
plasma abeta42 / abeta40
Intraindividual changes
Measured: 6 months
Safety and Tolerability of NPC1
Assessment of Adverse Events Related to NPC1 Treatment
Measured: Baseline through 6 months
Secondary outcomes (1)
plasma hsTNFalpha
intra-individual changes
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2025
- Study start1 Apr 2026
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Single arm, lead-in with blood-based biomarkers collected before and after treatment with a natural product combination (NPC1)
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gene L. Bowman, ND, MPH, Massachusetts General Hospital
- Investigators
- Gene Bowman, ND, MPH, Principal investigator, Harvard/Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07236190
- Sponsor's protocol ID
- 2025P000523
- Acronym
- NPC1-AD
- Status last verified
- Oct 2026
- First submitted
- 28 Oct 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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.
PubMed 41122812
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early-phase Biomarker-based Trial of NPC-1 for Alzheimer's Disease Pathology
- ClinicalTrials.gov ID
- NCT07236190
- Acronym / sponsor ID
- NPC1-AD / 2025P000523
- Keywords
- Open Label, Dietary Supplements, Alzheimer's Disease, Mild Cognitive Impairment (MCI), Intervention, early phase clinical trial, blood based biomarkers
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Apr 2026 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 19 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Single arm, lead-in with blood-based biomarkers collected before and after treatment with a natural product combination (NPC1)
| Arm | Type | Receives |
|---|---|---|
| Lead-in observational period | No intervention | –Serial blood-based biomarker collection |
| Active interventional period | Active comparator | Combination Product: natural product combination-1 (NPC1)Serial post treatment blood-based biomarkers |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age 55 and older, male and female;
- Subjective Cognitive Impairment or MCI or AD dementia per the Revised criteria for diagnosis and staging of Alzheimer's disease 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
Key exclusion criteria (26 listed)
- CDR > 2 MMSE < 16;
- Other significant CNS disease within the last 2 years (i.e., brain tumor, seizure disorder, subdural hematoma, cranial arteritis, cortical stroke) That would impact the participant's ability to complete the study;
- 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) or INR > 1.2 (1.3 or higher) or platelets < 100 K/uL at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| natural product combination-1 (NPC1)Also: parthenolide, ipriflavoneparthenolide plus ipriflavone | Combination product | Active interventional period |
Primary outcome
plasma p-tau217
Time frame: 6 months
Intra-individual changes from pre-treatment observational period to post-treatment interventional period
plasma glial fibrillary acidic protein
Time frame: 6 months
Intraindividual changes
plasma neurofilament light chain
Time frame: 6 months
Intra-individual changes
plasma abeta42 / abeta40
Time frame: 6 months
Intraindividual changes
Safety and Tolerability of NPC1
Time frame: Baseline through 6 months
Assessment of Adverse Events Related to NPC1 Treatment
1 secondary outcome
plasma hsTNFalpha
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Background: PubMed 41122812Dodge 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.
- Harvard-MGH-McCance Center for Brain Health-Clinical Trials PlatformLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Gene Bowman, ND, MPH principal investigator
Harvard/Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing natural product combination-1 (NPC1) in people with Alzheimer Disease and Mild Cognitive Impairment (MCI), run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Brianna Wang, MS (857-282-1520, npc1clinicaltrial@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
plasma p-tau217 (time frame: 6 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07236190, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.