Restoring Vascular and Insulin Function To Augment Anti-Amyloid Therapy in Alzheimer's Disease (REVITAA-ALZ)

August 24, 2026 updated by: Wake Forest University Health Sciences

REstoring Vascular and Insulin Function To Augment Anti-Amyloid Therapy in ALZheimer'ss Disease (REVITAA-ALZ): A Placebo-controlled Trial of Intranasal Insulin vs. Empagliflozin in Mild Cognitive Impairment (MCI) or Early Alzheimer's Disease (AD) Treated With Anti-Amyloid Targeting Therapy (Lecanemab or Donanemab)

The purpose of this study is to find out what effects (good and bad) the study medications (insulin or Empagliflozin) have on adults with mild memory impairment or early Alzheimer's disease who are clinically prescribed an anti-amyloid therapy compared to placebo.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The proposed pilot study will evaluate the efficacy, safety and tolerability of two therapeutic approaches: treatment with intranasal insulin in combination with anti-amyloid targeting therapy (ATT) and treatment with the sodium-glucose cotransporter type 2 inhibitor empagliflozin in combination with ATT, to correct bioenergetic and vascular dysfunction in adults with mild cognitive impairment due to Alzheimer's disease or mild dementia due to Alzheimer's disease.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Alzheimer's Disease Research Center (ADRC) Sticht Center for Healthy Aging
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Fluent in English
  • Diagnosis of mild cognitive impairment due to Alzheimer's disease or mild Alzheimer's disease via previously documented clinical assessment
  • Amyloid positive by PET or cerebrospinal fluid criteria
  • Stable medical condition for 3 months prior to screening visit
  • Stable medications for general medical conditions for 4 weeks prior to the screening and study visits (exceptions may be made on a case-by-case basis by study clinician)
  • Stable on Anti-Amyloid Targeting Therapy (lecanemab or donanemab) for at least 8 weeks prior to Baseline Visit
  • If receiving an acetylcholinesterase inhibitor (donepezil, rivastigmine, galantamine) or memantine or both, must be stable on a dose for at least 30 days prior to Baseline Visit
  • Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the study clinician
  • Participants must have a study partner who agrees to participate throughout the duration of the study. The study partner must have frequent and sufficient contact (approximately 10 hours per week) with the participant and be able to provide accurate information regarding the participant's cognitive and functional abilities.

Exclusion Criteria:

  • A diagnosis of dementia other than Alzheimer's disease
  • History of a clinically significant stroke, history of transient ischemic attack within 12 months, or any history of seizures
  • Current evidence or history in past two years of head injury with loss of consciousness, any major psychiatric disorder including psychosis, unstable major depressive disorder, bipolar disorder
  • Diabetes (type I or type II) insulin dependent and non-insulin dependent diabetes mellitus
  • Current or past regular use of insulin or any other anti-diabetic medication within 2 months of screening visit
  • Cancer within the past 2 years with the exception of non-melanoma skin cancers and non-metastatic prostate cancer that has been stable for at least 6 months
  • Pregnancy or possible pregnancy
  • Use of anticoagulants
  • Residence in a skilled nursing facility at screening
  • Use of an investigational agent within two months of screening visit
  • Regular use of alcohol, narcotics, anticonvulsants, anti-Parkinsonian medications, or any other exclusionary medications (exceptions may be made on a case-by-case basis by study clinician)
  • Any history of immunologic disease (e.g. lupus, rheumatoid arthritis, Crohn's disease) or systemic treatment with immunosuppressants, immunoglobulins, or monoclonal antibodies or their derivatives
  • History of a bleeding disorder that is not under adequate control, including a platelet count less than 50,000 or INR greater than 1.5
  • Contraindications for MRI, including claustrophobia or the presence of contraindicated metal implants/cardiac pacemaker
  • Baseline MRI Findings: More than four microhemorrhages defined as 10mm or less at the greatest diameter; A single macro hemorrhage greater than 10mm at greatest diameter; An area of superficial siderosis; Evidence of vasogenic edema; More than two lacunar infarcts or stroke involving a major vascular territory; Severe subcortical hyperintensities consistent with Fazekas score of 3; Evidence of amyloid beta-related angiitis (ABRA); Cerebral amyloid angiopathy (CAA); Cerebral contusion, encephalomalacia, brain aneurysm or other vascular malformations, central nervous system infection, brain tumor, or other major intracranial pathology that may cause cognitive impairment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Insulin and Empagliflozin Matching Placebo
Intranasal insulin 40 international units four times daily and empagliflozin matching placebo as add-on treatment to anti-amyloid therapy
Drug: Insulin
Intranasal insulin 40 international units four times daily
Drug: Empagliflozin Placebo
matching placebo for empagliflozin
Experimental: Empagliflozin and Insulin Matching Placebo
empagliflozin 10 mg every day and intranasal insulin matching placebo as add-on treatment to anti-amyloid therapy
Drug: Empagliflozin
empagliflozin 10 mg every day
Drug: Insulin Placebo
matching placebo for intranasal insulin
Experimental: Double Placebo
Placebo for intranasal insulin and placebo for empagliflozin as add-on treatment to anti-amyloid therapy
Drug: Empagliflozin Placebo
matching placebo for empagliflozin
Drug: Insulin Placebo
matching placebo for intranasal insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of treatment-related serious adverse events
Time Frame: Month 6
Number of treatment related serious adverse events experienced by participants during course of study
Month 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Alzheimer's Disease Assessment Scale-Cognition Score
Time Frame: baseline and month 6
The Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cog 14) is an evaluation of cognitive impairment in Alzheimer's disease including 14 different sub-tests that can be summed for a total score of 0-90. Higher scores indicate more severe cognitive impairment in Alzheimer's disease.
baseline and month 6
Modified Preclinical Alzheimer Cognitive Composite 5 Score
Time Frame: baseline and month 6
The modified Pre-clinical Alzheimer's Cognitive Composite (MPACC5) is a composite of several different cognitive measures designed to assess cognitive functioning in early Alzheimer's disease. Average Z scores will be calculated as baseline and post-intervention Z scores will be calculated using the baseline group mean and standard deviation. Total score range is -3 to 3. Negative z-scores reflect lower than expected cognitive functioning, positive z-scores reflect higher than expected cognitive functioning.
baseline and month 6
Montreal Cognitive Assessment Score
Time Frame: baseline and month 6
Montreal Cognitive Assessment (MoCA) is measure of global cognitive functioning used to detect cognitive impairment. It includes several sub-sections assessing various cognitive domains that are summed for a total score of 0-30. Higher scores indicate more intact cognitive functioning, lower scores indicate the presence of cognitive impairment.
baseline and month 6
Clinical Dementia Rating Scale Score
Time Frame: baseline and month 6
The Clinical Dementia Rating Scale measures dementia severity based on an interview with the patient and a caregiver. Scores ranging from 0 to 18 with higher scores indicating a higher severity of dementia.
baseline and month 6

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Alzheimer's disease biomarkers
Time Frame: from baseline to month 6
number of participants with change in Alzheimer's disease biomarkers
from baseline to month 6
change in hippocampal volume
Time Frame: from baseline to month 6
change in hippocampal assessed with MRI
from baseline to month 6
change in meta-ROI volume
Time Frame: from baseline to month 6
change in meta-ROI volumes assessed with MRI
from baseline to month 6
Change in Amyloid-Related Imaging Abnormalities (ARIA)
Time Frame: from baseline to month 6
number of participants with ARIA
from baseline to month 6

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wake Forest University Health Sciences

Investigators

  • Principal Investigator: Suzanne Craft, PhD, Wake Forest Alzheimer's Disease Research Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

August 5, 2026

First Submitted That Met QC Criteria

August 5, 2026

First Posted (Actual)

August 10, 2026

Study Record Updates

Last Update Posted (Actual)

August 25, 2026

Last Update Submitted That Met QC Criteria

August 24, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00144750

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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