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

NCT07756294 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: IRB00144750
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease

Keywords

mild cognitive impairment; mild dementia; insulin

Outcome Measures

Primary Outcomes (1)

• Number of treatment-related serious adverse events

  Number of treatment related serious adverse events experienced by participants during course of study

  Month 6

Secondary Outcomes (4)

• Alzheimer's Disease Assessment Scale-Cognition Score

  baseline and month 6

• Modified Preclinical Alzheimer Cognitive Composite 5 Score

  baseline and month 6

• Montreal Cognitive Assessment Score

  baseline and month 6

• Clinical Dementia Rating Scale Score

  baseline and month 6

Other Outcomes (4)

• Change in Alzheimer's disease biomarkers

  from baseline to month 6

• change in hippocampal volume

  from baseline to month 6

• change in meta-ROI volume

  from baseline to month 6

Study Arms (3)

Insulin and Empagliflozin Matching Placebo

EXPERIMENTAL

Intranasal insulin 40 international units four times daily and empagliflozin matching placebo as add-on treatment to anti-amyloid therapy

Drug: Insulin; Drug: Empagliflozin Placebo

Empagliflozin and Insulin Matching Placebo

EXPERIMENTAL

empagliflozin 10 mg every day and intranasal insulin matching placebo as add-on treatment to anti-amyloid therapy

Drug: Empagliflozin; Drug: Insulin Placebo

Double Placebo

EXPERIMENTAL

Placebo for intranasal insulin and placebo for empagliflozin as add-on treatment to anti-amyloid therapy

Drug: Insulin Placebo; Drug: Empagliflozin Placebo

Interventions

Empagliflozin DRUG

empagliflozin 10 mg every day

Empagliflozin and Insulin Matching Placebo

Insulin DRUG

Intranasal insulin 40 international units four times daily

Insulin and Empagliflozin Matching Placebo

Insulin Placebo DRUG

matching placebo for intranasal insulin

Double Placebo; Empagliflozin and Insulin Matching Placebo

Empagliflozin Placebo DRUG

matching placebo for empagliflozin

Double Placebo; Insulin and Empagliflozin Matching Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Wake Forest Alzheimer's Disease Research Center (ADRC) Sticht Center for Healthy Aging

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Insulin Resistance

Interventions

empagliflozin; Insulin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Suzanne Craft, PhD

  Wake Forest Alzheimer's Disease Research Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suzanne Craft, PhD

CONTACT

336-716-6463; mindadrcahwfb@advocatehealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 10, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: August 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)