Alzheimer Disease
Conditions
Keywords
mild cognitive impairment, mild dementia, insulin
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.
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.
Interventions
DRUGEmpagliflozin
empagliflozin 10 mg every day
DRUGInsulin
Intranasal insulin 40 international units four times daily
DRUGInsulin Placebo
matching placebo for intranasal insulin
matching placebo for empagliflozin
Sponsors
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of treatment-related serious adverse events | Month 6 | Number of treatment related serious adverse events experienced by participants during course of study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alzheimer's Disease Assessment Scale-Cognition Score | 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. |
| Modified Preclinical Alzheimer Cognitive Composite 5 Score | 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. |
| Montreal Cognitive Assessment Score | 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. |
| Clinical Dementia Rating Scale Score | 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. |
Countries
United States
Contacts
CONTACTSuzanne Craft, PhD
PRINCIPAL_INVESTIGATORSuzanne Craft, PhD
Wake Forest Alzheimer's Disease Research Center
Outcome results
None listed