Crownlands Observing Progression With Neurons Study

NCT07611396 | Recruiting

• 1 other identifier: CLNDS-16530
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

The CROWN-I Study is an observational study to learn about molecular features of Alzheimer's disease (AD) and mild cognitive impairment (MCI). The primary objective is to identify the molecular and genetic modules that differentiate patient subtypes and predict progression of AD. Participants will visit clinical sites to donate samples multiple times and perform virtual and in-person clinical assessments.

Conditions

Alzheimer s Disease; Mild Cognitive Impairment (MCI)

Keywords

alzheimer's; longitudinal; genetics; olfactory neurons; biomarkers

Outcome Measures

Primary Outcomes (2)

• Rate of change in CDR-SB

  The primary clinical outcomes are longitudinal changes from baseline in Clinical Dementia Rating - Sum of Boxes as administered by a qualified clinician. The CDR-SB evaluates six domains (memory, orientation, judgment, community affairs, home/hobbies, and personal care) for a total score ranging from 0 to 18, with increases indicating worsening impairment.

  From enrollment to the end of the observational period at 18 months or final visit

• Change in olfactory neuron transcriptomic profile

  Change from baseline in olfactory neurons measured by Gateway in transcriptomic pathways associated with AD by human genetics.

  From enrollment to the end of the observational period at 18 months or final visit

Secondary Outcomes (8)

• Change in p-tau217 in blood plasma

  From enrollment to the end of the observational period at 18 months or final visit

• Change in Aβ42/Aβ40 in blood plasma

  From enrollment to the end of the observational period at 18 months or final visit

• Change in whole blood transcriptomic profile

  From enrollment to the end of the observational period at 18 months or other endpoint

• Change in plasma proteomic profile

  From enrollment to the end of the observational period at 18 months or other endpoint

• Cross-sectional differences in olfactory neuron transcriptomics

  Baseline

Study Arms (3)

Alzheimer's disease (AD)

Participants with diagnosed Alzheimer's disease

Mild cognitive impairment (MCI)

Participants with diagnosed or apparent MCI

Cognitively normal

Participants who are cognitively normal

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

United States

You may qualify if:

• Informed consent provided by the participant or, where applicable, Legally Authorized Representative (LAR) or other substitute decision-maker where permitted by applicable law, as described in Section 8.2.
• Male or female, age ≥ 55 years at Screening.
• Fluency of subject and study partner in English sufficient to complete all cognitive and self-report assessments without interpreter assistance.
• Adequate visual and auditory acuity (with correction permitted) sufficient to complete neuropsychological testing.
• Not pregnant or lactating.
• Medications stable ≥ 4 weeks before screening.
• GDS-15 \< 6 (i.e., 0-5 inclusive; no current significant depression).
• Available study partner who has known the participant for ≥ 12 months, maintains \~10+ hours per week of in-person or telephone contact, and is willing to attend study visits and complete informant-rated assessments.
• Willing to complete olfactory brushing, smell testing, and venous blood draw.
• Willing to commit to baseline and follow-up visits across study duration.
• In the opinion of the Investigator, able to comply with the protocol-specified visit schedule and procedures for the full study duration.

You may not qualify if:

• Current or active clinically significant neurological disorder (in the opinion of the Investigator) other than the disorders in the study arms, including but not limited to:
• Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, Huntington's disease, prion disease, multi-infarct dementia, normal pressure hydrocephalus, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, significant head trauma with persistent deficits, or known structural brain abnormalities.
• Active or unstable major psychiatric illness (DSM-5 schizophrenia spectrum, bipolar I, or severe major depressive disorder with active suicidality) within 6 months prior to Screening; history of schizophrenia at any time.
• Psychotic features, agitation, or behavioral problems within the last 3 months that could interfere with protocol compliance.
• Current substance use disorder (DSM-5 moderate or severe), or alcohol use disorder within 24 months prior to Screening.
• Active malignancy under treatment, or malignancy with expected survival \< 30 months (excluding non-melanoma skin cancer and localized prostate cancer on active surveillance).
• Participation in studies collecting neuropsychological measures more than once per year.
• Presence of previous nasal surgery or other anatomical abnormalities that could interfere with the procedure on both sides of the nose, at the discretion of the clinician administering the Olfactory Brushing.
• Active respiratory infection or recent history of respiratory infection within the past two weeks.
• Known allergy or adverse reaction to topical anesthetics or decongestants used in the study (e.g., lidocaine, tetracaine, oxymetazoline).
• Any other medical or psychiatric condition or lab abnormality that, in the opinion of the Investigator, might preclude participation or render the participant unsuitable for study enrollment.
• No subjective cognitive complaint reported by participant AND no cognitive -complaint reported by study partner.
• No current or prior clinical diagnosis of MCI, Alzheimer's disease, or any other dementia, and no current clinical diagnosis of a neurological or neuropsychiatric disease.
• MMSE score ≥ 27 / 30 at Screening.
• Global Clinical Dementia Rating (CDR) = 0 at Screening.

Sponsors & Collaborators

• Crownlands: lead

Study Sites (1)

Capital Neurology

Germantown, Maryland, 20876, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

olfactory neuron biopsy, whole blood, blood plasma, dna isolates

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Mason Sanfilippo, MS

CONTACT

(415) 623-8635; m.sanfilippo@crownlands.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2026
• First Posted: May 28, 2026
• Study Start: May 19, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: June 4, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)