Dapagliflozin In Alzheimer's Disease
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Detailed description: 
      This is a double-blind, randomized, placebo-controlled, parallel group, 12-week study
      performed at a single site (University of Kansas Alzheimer's Disease Center) to investigate
      the effect of dapagliflozin in participants with probable AD (MMSE 15-26 inclusive). A total
      of 48 participants will be enrolled with 2:1 randomization to 10mg dapagliflozin once daily
      (n=32) for 12 weeks vs matching placebo (n=16).

      The primary objective of the study is to assess the effect of 12 weeks of 10mg dapagliflozin
      once daily on cerebral NAA (a proxy measure of mitochondrial mass) in participants with AD.

      Procedures will include phlebotomy, urine collection, MRI/MRS, FDG-PET, cognitive testing,
      DEXA scanning, and indirect calorimetry at baseline and 12 weeks to assess these outcomes:

        -  N Acetyl-Aspartate (NAA): Cerebral NAA (as measured by MRS) and Systemic NAA levels (in
           blood and urine)

        -  Cerebral metabolism (by FDG PET)

        -  Systemic metabolic effects: Lipids (total cholesterol, LDL, HDL), Plasma
           beta-hydroxybutyrate, Insulin resistance (Hemoglobin A1c, glucose and insulin during
           tolerance testing), Catabolic/Anabolic state [activated AKT and MTOR], Mitochondrial
           function measures [platelet cytochrome oxidase and citrate synthase], Inflammatory
           mechanisms [MCP-1, eotaxin, TNF alpha, CRP], Body composition (DEXA scanning for fat and
           lean mass), Resting metabolic rate (indirect calorimetry),

        -  Cognitive effects will be assessed at baseline and week 12 using the Alzheimer's Disease
           Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14) and individual tests of Logical
           Memory I and II, Trailmaking A and B, and Stroop Word Color Test.

        -  12 participants will be enrolled in an optional MRI/MRS sub-study with repeat MRI/MRS
           prior to randomization to assess scan-rescan reliability of the NAA measure.

      Safety and tolerability of dapagliflozin (10mg daily) will be monitored throughout the study
      and formally at every study visit to assess the incidence and severity of AEs and the rate of
      discontinuations due to AEs. Safety assessments will include measuring vital signs and body
      weight, safety labs (including a comprehensive metabolic panel [CMP] and complete blood count
      [CBC] with differential) and physical and neurological examinations at screening and at end
      of treatment (EOT).
    

Intervention name(s): Dapagliflozin; Placebo
Intervention type(s): Drug; Other
Intervention description(s): 10 mg oral tablets taken once daily for 12 weeks; Placebo tablet (matched in size and color to active tablet) taken once daily for 12 weeks
Other intervention name(s): Farxiga
Intervention MeSH terms: Dapagliflozin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment