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

Korábbi kezelés

• 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)

Más betegség

• 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;
• Major depressive disorder or anxiety within the last year; Schizophrenia, bipolar disorder or other major psychiatric disorder defined by DSM-IV criteria
• Unstable or significantly symptomatic CVD (e.g. CAD with frequent angina, CHF with dyspnea at rest)
• Hypertension: defined as uncontrolled BP > 160/100
• Diabetes mellitus that requires insulin injections
• 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
• Participation in any Alzheimer's Disease interventional trial. Participation in other non-AD related trials will be evaluated at the discretion of the investigator

Laborértékek

• 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
• 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).

Egyéb

• CDR > 2 MMSE < 16;
• Alcohol or substance abuse according to DSM-IV criteria within the last 2 years
• Clinical symptomatic orthostatic hypotension
• Hachinski ischemic score > or = to 4
• 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

• 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;
• 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)