A Pilot Open Labeled Study of Tacrolimus in Alzheimer's Disease.

NCT04263519 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 2019P003904
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A Pilot open labeled study of Tacrolimus in Alzheimer's Disease.

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• CSF biomarkers of target engagement, AD pathology, and neurodegeneration

  Evaluate effect of tacrolimus on molecular markers of target engagement (calcineurin/NFAT mediated inflammatory markers IL-2, IL-6, IFNβ and YKL-40), AD pathology (amyloid-β, tau, phospho-tau) and neurodegeneration (neurofilament-light, neurogranin). We will measure change from baseline in all CSF biomarkers following 12 weeks of steady treatment.

  Baseline and 12 weeks

Secondary Outcomes (8)

• Blood biomarkers of target engagement, AD pathology, and neurodegeneration.

  Baseline and 12 weeks

• Structural neuroimaging of Hippocampal volume.

  Baseline and 12 weeks

• Functional neuroimaging of default mode network connectivity.

  Baseline and 12 weeks

• Electroencephalograms (EEG) spectral power

  Baseline and 12 weeks

• Montreal Cognitive Assessment (MoCA)

  Baseline and 12 weeks

Study Arms (2)

Low Serum Level

ACTIVE COMPARATOR

Stable Blood Tacrolimus of 2-5 ng/ml.

Drug: Tacrolimus

High Serum Level

ACTIVE COMPARATOR

Stable Blood Tacrolimus of 5.1-10 ng/ml.

Drug: Tacrolimus

Interventions

Tacrolimus DRUG

Oral Immunosuppressant

High Serum Level; Low Serum Level

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Study subjects meeting all of the following criteria will be allowed to enroll in the study:
• Age 55-85 inclusive, male or female.
• Diagnosis of MCI or dementia due to AD as shown by positive AD biomarker (CSF or neuroimaging).
• Education level, English language skills and literacy indicates subject will be able to complete all assessments.
• Willing and able to complete all assessment and study procedures, including phlebotomies, lumbar punctures, MRIs, neurocognitive testing.
• Subject has a study partner with at least two days of contact per week and willingness to assist with subject's research activities.
• If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline.

You may not qualify if:

• Subjects meeting any of the following criteria during the screening evaluation will be excluded:
• Allergy or hypersensitivity to tacrolimus.
• Any specific CNS disease other than suspected AD, such as major clinical stroke, brain tumor, normal pressure hydrocephalus, multiple sclerosis, significant head trauma with persistent neurological of cognitive deficits or complaints, Parkinson's disease, frontotemporal dementia, and/or other neurodegenerative diseases.
• Any significant systemic illness or clinically significant unstable medical condition that could affect subject safety or compliance with the study; including but not limited to any active infection, active malignancy except non-melanomatous skin cancers, cirrhosis, active hepatitis, uncontrolled diabetes (A1c \>8), AIDS, common variable immunodeficiency, conditions treated with biologics, uncontrolled hypertension, chronic kidney disease with an eGFR \<45 ml/min, Platelets \< 100K, Hgb \<9.
• History of alcohol or other substance abuse or dependence with the past two years.
• Major active psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year.
• Current suicidal ideation or history of suicide attempt.
• Contraindications to undergo MRI studies:
• History of a cardiac pacemaker or pacemaker wires,
• Metallic particles in the body,
• Vascular clips in the head,
• Prosthetic heart valves, or
• Severe claustrophobia impeding ability to participate in an imaging study.
• MRI findings that show one or more of the following:
• More than 4 incidental microhemorrhages,

Sponsors & Collaborators

• Massachusetts General Hospital: lead

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Manager Director Phsycian

Study Record Dates

• First Submitted: January 23, 2020
• First Posted: February 10, 2020
• Study Start: December 1, 2021
• Primary Completion: December 1, 2022
• Study Completion: January 1, 2023
• Last Updated: September 27, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share