Alzheimer DiseasePhase 2NCT04263519
A Pilot Open Labeled Study of Tacrolimus in Alzheimer's Disease.
A Phase 2 study testing Tacrolimus in people with Alzheimer Disease and Mild Cognitive Impairment, run by Massachusetts General Hospital.
Trial summary
A Pilot open labeled study of Tacrolimus in Alzheimer's Disease. Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer Disease, Mild Cognitive Impairment
- What is being tested?
- Tacrolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2021to 1 Jan 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 28Show fewer
- 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,
- Incidental lacunar infarcts with attributable signs or symptoms and with history of stroke,
- Incidental meningiomas with attributable signs or symptoms, or
- Newly recognized meningioma.
- Laboratory abnormalities in B12, TSH, or other common laboratory parameters that may contribute to cognitive dysfunction.
- Laboratory abnormalities in PT-INR, CBC, electrolytes, magnesium, LFTs, BUN, Cr or others, or abnormalities in ECG posing risk to treatment with tacrolimus.
- 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.
- Current use of medications that interact with tacrolimus (protease inhibitors, macrolides, rifampin, barbiturates, phenytoin, or azoles).
- Inability to avoid any dietary supplements that could interact with tacrolimus metabolism.
- Inability to avoid grapefruit and grapefruit juice.
- 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.
- Discontinuation of cholinesterase inhibitor or memantine within one month (28 days) prior to baseline visit.
- Females who are pregnant, lactating or of child-bearing potential
- -
About this study
Official title: A Pilot Open Labeled Study of Tacrolimus to Assess it's Effects on Bio-markers of Mild Cognitive Impairment and Alzheimer's Disease
A Pilot open labeled study of Tacrolimus in Alzheimer's Disease.
Read the 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
- Being tested
- Tacrolimus
- 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.
TacrolimusDrug
Oral Immunosuppressant
| Study group | Role | What they receive |
|---|---|---|
| Low Serum Level | Active comparator | Stable Blood Tacrolimus of 2-5 ng/ml. Receives: Drug: Tacrolimus |
| High Serum Level | Active comparator | Stable Blood Tacrolimus of 5.1-10 ng/ml. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 12 weeks
Secondary outcomes (8)
Blood 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 blood biomarkers following 12 weeks of steady treatment.
Measured: Baseline and 12 weeks
Structural neuroimaging of Hippocampal volume.
Evaluate effect of tacrolimus on size of different brain regions using Magnetic Resonance Imaging (MRI). We will measure change from baseline after 12 weeks of treatment.
Measured: Baseline and 12 weeks
Functional neuroimaging of default mode network connectivity.
Evaluate effect of tacrolimus on blood flow to different brain regions using functional MRI (fMRI). We will measure change from baseline after 12 weeks of treatment.
Measured: Baseline and 12 weeks
Electroencephalograms (EEG) spectral power
Evaluate effect of tacrolimus on resting state EEG frequency using the linear power spectral density technique. We will measure change from baseline after 12 weeks of treatment.
Measured: Baseline and 12 weeks
Montreal Cognitive Assessment (MoCA)
Evaluate effect of tacrolimus on major domains of cognition (score range 0-30, high is better). We will measure change from baseline after 12 weeks of treatment.
Measured: Baseline and 12 weeks
Neuropsychiatric Inventory Questionnaire (NPIQ)
Evaluate effect of tacrolimus on neuropsychiatric symptoms as rated by a study partner/informant (score range 0-80, high is worse). We will measure change from baseline after 4, 8, and 12 weeks of treatment.
Measured: Baseline, 4 weeks, 8 weeks and 12 weeks
Functional Activities Questionnaire (FAQ)
Evaluate effect of tacrolimus on ability to daily functional ability as reported by study partner/informant (score range (0-30, low is better). We will measure change from baseline after 4, 8, and 12 weeks of treatment.
Measured: Baseline, 4 weeks, 8 weeks and 12 weeks
Repeated Battery for the Assessment of Neuropsychological Status
Evaluate the effect of tacrolimus on several domains of cognitive function (score range 40-160, higher is better). We will measure change from baseline after 4, 8, and 12 weeks of treatment.
Measured: Baseline, 4 weeks, 8 weeks and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2020
- Study start1 Dec 2021 (estimated)
- Primary completion1 Dec 2022 (estimated)
- Study completion1 Jan 2023 (estimated)
Why it stopped: Covid restrictions
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven E Arnold, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04263519
- Sponsor's protocol ID
- 2019P003904
- Status last verified
- Sep 2021
- First submitted
- 23 Jan 2020
- Last updated
- 27 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Open Labeled Study of Tacrolimus to Assess it's Effects on Bio-markers of Mild Cognitive Impairment and Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04263519
- Acronym / sponsor ID
- 2019P003904
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Covid restrictions
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 1 Dec 2021 (estimated)
- Primary completion
- 1 Dec 2022 (estimated)
- Study completion
- 1 Jan 2023 (estimated)
- First posted
- 10 Feb 2020 (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.
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:
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low Serum Level | Active comparator | Drug: TacrolimusStable Blood Tacrolimus of 2-5 ng/ml. |
| High Serum Level | Active comparator | Drug: TacrolimusStable Blood Tacrolimus of 5.1-10 ng/ml. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (28 listed)
- 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.
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 |
|---|---|---|
| TacrolimusOral Immunosuppressant | Drug | High Serum Level, Low Serum Level |
Primary outcome
CSF biomarkers of target engagement, AD pathology, and neurodegeneration
Time frame: Baseline and 12 weeks
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.
8 secondary outcomes
Blood biomarkers of target engagement, AD pathology, and neurodegeneration.
Time frame: Baseline and 12 weeks
Structural neuroimaging of Hippocampal volume.
Time frame: Baseline and 12 weeks
Functional neuroimaging of default mode network connectivity.
Time frame: Baseline and 12 weeks
Electroencephalograms (EEG) spectral power
Time frame: Baseline and 12 weeks
Montreal Cognitive Assessment (MoCA)
Time frame: Baseline and 12 weeks
Neuropsychiatric Inventory Questionnaire (NPIQ)
Time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
Functional Activities Questionnaire (FAQ)
Time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
Repeated Battery for the Assessment of Neuropsychological Status
Time frame: Baseline, 4 weeks, 8 weeks and 12 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2021.
- Individual participant dataSharing planned: No
Related trials for Alzheimer Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tacrolimus in people with Alzheimer Disease and Mild Cognitive Impairment, run by Massachusetts General Hospital.
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 7 inclusion and 28 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: withdrawn, as of the sponsor's last update on 27 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CSF biomarkers of target engagement, AD pathology, and neurodegeneration (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Sep 2021.