Dapagliflozin In Alzheimer's Disease

• Status: Recruiting
• Trial end date: 2022-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a pilot randomized controlled trial in individuals with probable Alzheimer's disease testing the effects of 10 mg dapagliflozin, taken daily for 12 weeks, on cerebral n-acetyl aspartate (NAA) levels using magnetic resonance spectroscopy (MRS). The investigators will also examine the safety and tolerability of dapagliflozin and explore the effects on systemic NAA levels in blood and urine, cerebral metabolism (fluorodeoxyglucose [FDG] PET), systemic metabolic biomarkers that indicate and quantify secondary metabolic effects, and cognitive performance.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jeff Burns, MD
• Treatments: Dapagliflozin

Criteria

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures.

2. Have a diagnosis of probable AD per McKhann et al. criteria

3. Have a body mass index (BMI) ≥23

4. Age 50-85

5. Have a Mini Mental Status Exam (MMSE) score of 15-26 (inclusive) at screening visit

6. Have a reliable and competent study partner who is willing to accompany the participant to all study visits, monitor compliance of study medication administration, and observe/report any changes in the participant's health throughout the study duration

7. Are on stable doses of concurrent medications for at least 4 weeks prior to the screening visit

8. Speaks English as his/her primary language.

9. Females of child-bearing potential (i.e., pre-menopausal) must have a negative urine pregnancy test at the screening visit and must agree to use of contraception throughout the trial and for 30 days after the last dose of study medication. The approved methods of contraception are abstinence, the consistent use of an approved oral contraceptive (birth control pill or "the pill"), an intrauterine device (IUD), hormonal implants, contraceptive injection, double barrier method (diaphragm with spermicidal gel or condom with contraceptive foam).

Exclusion Criteria:

1. Received an investigational product in another clinical study during the last 4 weeks prior to screening

2. Diagnosis of Type 1 diabetes

3. Diagnosis of Type 2 diabetes treated with insulin, sulfonylureas, glucagon like peptide1 receptor agonists (GLP-1), thiazolidinedione (TZD) or SGLT2 inhibitors (metformin monotherapy is allowed).

4. Estimated Glomerular Filtration Rate (eGFR; MDRD) <45 mL/min at screening or unstable renal disease.

5. Any condition when MRI is contraindicated such as, but not limited to, having a pacemaker or claustrophobia.

6. Severe hepatic injury and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN. Total bilirubin >2.0 mg/dL (34.2 μmol/L)

7. Intolerance or allergy to dapaglifozin or any other SGLT2 inhibitor or any other substance in the tablets.

8. Dementia due to causes other than AD

9. History of recurrent urinary tract infection

10. Active mycotic genital infection

11. History of bladder cancer

12. History of diabetic ketoacidosis

13. Potentially confounding, serious, or unstable medical conditions such as:

1. cancer within the past 3 years (except basal cell, squamous cell, or localized prostate cancer)

2. a recent cardiac event (i.e. heart attack, angioplasty, etc. within the 3 months prior to screening visit)

3. other conditions that pose a potential safety risk or confounding factor in the investigator's opinion

14. Any abnormal physical examination assessment or vital sign assessment at the screening visit that is deemed to be clinically significant by the principal investigator.

15. Any abnormal clinical laboratory test result at the screening visit that is deemed to be clinically significant by the principal investigator.