Dapagliflozin In Alzheimer's Disease
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|ClinicalTrials.gov Identifier: NCT03801642|
Recruitment Status : Recruiting
First Posted : January 11, 2019
Last Update Posted : January 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease||Drug: Dapagliflozin Other: Placebo||Phase 1 Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Randomized Controlled Pilot Trial Of Dapagliflozin In Alzheimer's Disease|
|Estimated Study Start Date :||February 2019|
|Estimated Primary Completion Date :||October 2020|
|Estimated Study Completion Date :||October 2020|
10 mg dapagliflozin oral tablet taken once daily for 12 weeks
10 mg oral tablets taken once daily for 12 weeks
Other Name: Farxiga
Placebo Comparator: Matching placebo
Placebo oral tablet taken once daily for 12 weeks
Placebo tablet (matched in size and color to active tablet) taken once daily for 12 weeks
- Cerebral N Acetyl-Aspartate (NAA) [ Time Frame: 12 weeks ]Cerebral NAA concentration via Magnetic Resonance Spectroscopy (MRS)
- Systemic NAA levels [ Time Frame: 12 weeks ]NAA concentration levels in blood and urine using UPLC-MS/MS method
- FDG PET Metabolism (Standard Uptake Value Ratio) [ Time Frame: 12 weeks ]FDG PET measures reflecting cerebral metabolism standardized to the uptake value of the cerebellum and standardized uptake value ratios (SUVR) will be calculated from native-space ROIs.
- Total Cholesterol [ Time Frame: 12 weeks ]Total cholesterol level
- LDL Cholesterol [ Time Frame: 12 weeks ]LDL cholesterol level
- HDL Cholesterol [ Time Frame: 12 weeks ]HDL cholesterol level
- Plasma beta-hydroxybutyrate [ Time Frame: 12 weeks ]Plasma beta-hydroxybuteryate levels (ketones)
- Hemoglobin A1C [ Time Frame: 12 weeks ]Hemoglobin A1C
- Glucose Area Under the Curve [ Time Frame: 12 weeks ]Glucose area under the curve will be calculated based on glucose levels during a 120 minute oral glucose tolerance test.
- Insulin Area Under the Curve [ Time Frame: 12 weeks ]Insulin area under the curve will be calculated based on insulin levels during a 120 minute oral glucose tolerance test.
- Activated AKT levels [ Time Frame: 12 weeks ]Activated AKT will be measured in lymphocytes immunochemically.
- MTOR Phosphorylation [ Time Frame: 12 weeks ]MTOR phosphorylation will be measured in lymphocytes
- Platelet Cytochrome Oxidase activity [ Time Frame: 12 weeks ]Cytochrome Oxidase Vmax activity is determined as a pseudo first order-rate constant (sec-1/mg protein) by measuring the oxidation of reduced cytochrome c at 550 nm
- Monocyte Chemotactic Protein 1 (MCP-1) [ Time Frame: 12 weeks ]MCP-1, a measure of inflammation, will be measured in platelet free plasma using ELISA.
- Eotaxin-1 [ Time Frame: 12 weeks ]Eotaxin-1, a measure of inflammation, will be measured in platelet free plasma using ELISA.
- Tumor Necrosis Factor (TNF) - alpha [ Time Frame: 12 weeks ]TNF-alpha, a measure of inflammation, will be measured in platelet free plasma using ELISA.
- C-Reactive Protein (CRP) [ Time Frame: 12 weeks ]CRP, a measure of inflammation, will be measured in platelet free plasma using ELISA.
- Total fat mass [ Time Frame: 12 weeks ]Body composition will be assessed using dual energy x-ray absorptiometry (GE Lunar iDEXA) to determine fat-free mass, fat mass, and percent body fat at baseline, and week 12
- Total lean mass [ Time Frame: 12 weeks ]Body composition will be assessed using dual energy x-ray absorptiometry (GE Lunar iDEXA) to determine fat-free mass, fat mass, and percent body fat at baseline, and week 12
- Resting Metabolic Rate [ Time Frame: 12 weeks ]Resting metabolic rate will be assessed using indirect calorimetry which measures CO2 production and O2 consumption to calculate total energy produced.
- ADAS-Cog 14 [ Time Frame: 12 weeks ]Cognitive performance as measured by total score on the ADAS-cog 14.
- Trailmaking B [ Time Frame: 12 weeks ]Cognitive performance as measured by Trailmaking B
- Stroop Word Color Test [ Time Frame: 12 weeks ]Cognitive performance on the Stroop Word Color test.
- Logical Memory II [ Time Frame: 12 weeks ]Memory performance as measured by the Logical Memory II test.
- Number of Adverse Events [ Time Frame: 14 weeks ]Total number of adverse events considered related to the study medication
- Number of Discontinuations due to Adverse Events [ Time Frame: 14 weeks ]Number of participants who stop taking the study medication due to adverse events
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03801642
|Contact: Erin Schwartz||(913) firstname.lastname@example.org|
|Contact: Annette Becker||(913) email@example.com|
|United States, Kansas|
|University of Kansas Medical Center||Recruiting|
|Kansas City, Kansas, United States, 66160|
|Principal Investigator:||Jeffrey Burns, MD||University of Kansas Medical Center|