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

NCT ID: NCT04263519

Last Updated: 2021-09-27

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-01
• Study Completion Date: 2023-01-01

Brief Summary

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

Detailed Description

This study will investigate the neurobiological effect of tacrolimus in persons with MCI and dementia due to AD by measuring biomarkers of target engagement in immune response, amyloid-b, tau and neurodegeneration in CSF, functional connectivity with MRI and EEG, and cognition. Study objectives include:

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low Serum Level

Stable Blood Tacrolimus of 2-5 ng/ml.

Group Type: ACTIVE_COMPARATOR

Tacrolimus

Intervention Type: DRUG

Oral Immunosuppressant

High Serum Level

Stable Blood Tacrolimus of 5.1-10 ng/ml.

Group Type: ACTIVE_COMPARATOR

Tacrolimus

Intervention Type: DRUG

Oral Immunosuppressant

Interventions

Tacrolimus

Oral Immunosuppressant

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Study subjects meeting all of the following criteria will be allowed to enroll in the study:

1. Age 55-85 inclusive, male or female.

2. Diagnosis of MCI or dementia due to AD as shown by positive AD biomarker (CSF or neuroimaging).

3. Education level, English language skills and literacy indicates subject will be able to complete all assessments.

4. Willing and able to complete all assessment and study procedures, including phlebotomies, lumbar punctures, MRIs, neurocognitive testing.

5. Subject has a study partner with at least two days of contact per week and willingness to assist with subject's research activities.

6. If on cholinesterase inhibitor and/or memantine, doses are stable for 3 months prior to baseline.

Exclusion Criteria

Subjects meeting any of the following criteria during the screening evaluation will be excluded:

1. Allergy or hypersensitivity to tacrolimus.

2. 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.

3. 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.

4. History of alcohol or other substance abuse or dependence with the past two years.

5. Major active psychiatric illness (e.g. depression, bipolar disorder, obsessive compulsive disorder, schizophrenia) within the previous year.

6. Current suicidal ideation or history of suicide attempt.

7. Contraindications to undergo MRI studies:

1. History of a cardiac pacemaker or pacemaker wires,

2. Metallic particles in the body,

3. Vascular clips in the head,

4. Prosthetic heart valves, or

5. Severe claustrophobia impeding ability to participate in an imaging study.

8. MRI findings that show one or more of the following:

1. More than 4 incidental microhemorrhages,

2. Incidental lacunar infarcts with attributable signs or symptoms and with history of stroke,

3. Incidental meningiomas with attributable signs or symptoms, or

4. Newly recognized meningioma.

9. Laboratory abnormalities in B12, TSH, or other common laboratory parameters that may contribute to cognitive dysfunction.

10. Laboratory abnormalities in PT-INR, CBC, electrolytes, magnesium, LFTs, BUN, Cr or others, or abnormalities in ECG posing risk to treatment with tacrolimus.

11. Current use of medications with psychoactive properties (e.g., anticholinergics, antihistamines, antipsychotics, sedative hypnotics, anxiolytics) that may deleteriously affect cognition in the judgement of the investigator.

12. Current use of medications that interact with tacrolimus (protease inhibitors, macrolides, rifampin, barbiturates, phenytoin, or azoles).

13. Inability to avoid any dietary supplements that could interact with tacrolimus metabolism.

14. Inability to avoid grapefruit and grapefruit juice.

15. Use of other small molecule or device-based investigational agents one month prior to entry and for the duration of the trial; or participation in any immunotherapy clinical trial within three months prior to baseline visit.

16. Discontinuation of cholinesterase inhibitor or memantine within one month (28 days) prior to baseline visit.

17. Females who are pregnant, lactating or of child-bearing potential

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• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Steven E Arnold

Manager Director Phsycian

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

2019P003904

Identifier Type: -

Identifier Source: org_study_id