Dapagliflozin In Alzheimer's Disease

NCT03801642 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: Dapa in AD
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Ratio of Cerebral N Acetyl-Aspartate (NAA) / Cerebral Creatine

  Estimated mean change from baseline in the ratio of cerebral NAA/ cerebral Creatine as measured by MRI Spectroscopy.

  12 weeks

Other Outcomes (25)

• Systemic NAA Levels

  12 weeks

• FDG PET Metabolism (Standard Uptake Value Ratio)

  12 weeks

• Total Cholesterol

  12 weeks

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

10 mg dapagliflozin oral tablet taken once daily for 12 weeks

Drug: Dapagliflozin

Matching placebo

PLACEBO COMPARATOR

Placebo oral tablet taken once daily for 12 weeks

Other: Placebo

Interventions

Dapagliflozin DRUG

10 mg oral tablets taken once daily for 12 weeks

Also known as: Farxiga

Dapagliflozin

Placebo OTHER

Placebo tablet (matched in size and color to active tablet) taken once daily for 12 weeks

Matching placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• Have a diagnosis of probable AD per McKhann et al. criteria
• Have a body mass index (BMI) ≥23
• Age 50-85
• Have a Mini Mental Status Exam (MMSE) score of 15-26 (inclusive) at screening visit
• 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
• Are on stable doses of concurrent medications for at least 4 weeks prior to the screening visit
• Speaks English as his/her primary language.
• 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).

You may not qualify if:

• Received an investigational product in another clinical study during the last 4 weeks prior to screening
• Diagnosis of Type 1 diabetes
• 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).
• Estimated Glomerular Filtration Rate (eGFR; MDRD) \<45 mL/min at screening or unstable renal disease.
• Any condition when MRI is contraindicated such as, but not limited to, having a pacemaker or claustrophobia.
• 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)
• Intolerance or allergy to dapaglifozin or any other SGLT2 inhibitor or any other substance in the tablets.
• Dementia due to causes other than AD
• History of recurrent urinary tract infection
• Active mycotic genital infection
• History of bladder cancer
• History of diabetic ketoacidosis
• Potentially confounding, serious, or unstable medical conditions such as:
• cancer within the past 3 years (except basal cell, squamous cell, or localized prostate cancer)
• a recent cardiac event (i.e. heart attack, angioplasty, etc. within the 3 months prior to screening visit)

Sponsors & Collaborators

• Jeff Burns, MD: lead

Study Sites (1)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Dr. Jeffrey Burns
• Organization: University of Kansas Medical Center

jburns2@kumc.edu

913-588-0555

Study Officials

• Jeffrey Burns, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 21, 2018
• First Posted: January 11, 2019
• Study Start: January 29, 2019
• Primary Completion: July 7, 2022
• Study Completion: July 7, 2022
• Last Updated: June 13, 2024
• Results First Posted: June 13, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)