Trial Outcomes & Findings for Dapagliflozin In Alzheimer's Disease (NCT NCT03801642)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

46 participants

Primary outcome timeframe

12 weeks

Results posted on

2024-06-13

Participant Flow

Participant milestones

Participant milestones
Measure	Dapagliflozin 10 mg dapagliflozin oral tablet taken once daily for 12 weeks Dapagliflozin: 10 mg oral tablets taken once daily for 12 weeks	Matching Placebo Placebo oral tablet taken once daily for 12 weeks Placebo: Placebo tablet (matched in size and color to active tablet) taken once daily for 12 weeks
Overall Study STARTED	30	16
Overall Study COMPLETED	30	16
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dapagliflozin In Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dapagliflozin n=30 Participants 10 mg dapagliflozin oral tablet taken once daily for 12 weeks Dapagliflozin: 10 mg oral tablets taken once daily for 12 weeks	Matching Placebo n=16 Participants Placebo oral tablet taken once daily for 12 weeks Placebo: Placebo tablet (matched in size and color to active tablet) taken once daily for 12 weeks	Total n=46 Participants Total of all reporting groups
Age, Continuous	69.8 years STANDARD_DEVIATION 7.9 • n=5 Participants	71.8 years STANDARD_DEVIATION 8.1 • n=7 Participants	71.1 years STANDARD_DEVIATION 8.0 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	12 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	13 Participants n=7 Participants	37 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	16 Participants n=7 Participants	44 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: All participants completing MRI spectroscopy at baseline and week-12, where data for both scans passed the data quality criteria.

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

Outcome measures

Outcome measures
Measure	Dapagliflozin n=28 Participants 10 mg dapagliflozin oral tablet taken once daily for 12 weeks Dapagliflozin: 10 mg oral tablets taken once daily for 12 weeks	Matching Placebo n=15 Participants Placebo oral tablet taken once daily for 12 weeks Placebo: Placebo tablet (matched in size and color to active tablet) taken once daily for 12 weeks
Ratio of Cerebral N Acetyl-Aspartate (NAA) / Cerebral Creatine	1.49 Ratio Standard Deviation 0.11	1.42 Ratio Standard Deviation 0.09

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

NAA concentration levels in blood and urine using UPLC-MS/MS method

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Total cholesterol level

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

LDL cholesterol level

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

HDL cholesterol level

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Plasma beta-hydroxybuteryate levels (ketones)

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Hemoglobin A1C

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Glucose area under the curve will be calculated based on glucose levels during a 120 minute oral glucose tolerance test.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Insulin area under the curve will be calculated based on insulin levels during a 120 minute oral glucose tolerance test.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Activated AKT will be measured in lymphocytes immunochemically.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

MTOR phosphorylation will be measured in lymphocytes

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

MCP-1, a measure of inflammation, will be measured in platelet free plasma using ELISA.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Eotaxin-1, a measure of inflammation, will be measured in platelet free plasma using ELISA.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

TNF-alpha, a measure of inflammation, will be measured in platelet free plasma using ELISA.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

CRP, a measure of inflammation, will be measured in platelet free plasma using ELISA.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Resting metabolic rate will be assessed using indirect calorimetry which measures CO2 production and O2 consumption to calculate total energy produced.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Cognitive performance as measured by total score on the ADAS-cog 14.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Cognitive performance as measured by Trailmaking B

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Cognitive performance on the Stroop Word Color test.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 weeks

Memory performance as measured by the Logical Memory II test.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 14 weeks

Total number of adverse events considered related to the study medication

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 14 weeks

Number of participants who stop taking the study medication due to adverse events

Outcome measures

Outcome data not reported

Adverse Events

Dapagliflozin

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Matching Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Jeffrey Burns

University of Kansas Medical Center

Phone: 913-588-0555

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dapagliflozin n=30 participants at risk 10 mg dapagliflozin oral tablet taken once daily for 12 weeks Dapagliflozin: 10 mg oral tablets taken once daily for 12 weeks	Matching Placebo n=16 participants at risk Placebo oral tablet taken once daily for 12 weeks Placebo: Placebo tablet (matched in size and color to active tablet) taken once daily for 12 weeks
Respiratory, thoracic and mediastinal disorders Cold	10.0% 3/30 • Number of events 3 • Data was collected from week 0 to week 12 Does not differ	12.5% 2/16 • Number of events 2 • Data was collected from week 0 to week 12 Does not differ
Skin and subcutaneous tissue disorders Basal Cell Carcinoma Removal	6.7% 2/30 • Number of events 2 • Data was collected from week 0 to week 12 Does not differ	0.00% 0/16 • Data was collected from week 0 to week 12 Does not differ
Renal and urinary disorders Discomfort with Urination	10.0% 3/30 • Number of events 3 • Data was collected from week 0 to week 12 Does not differ	0.00% 0/16 • Data was collected from week 0 to week 12 Does not differ
Respiratory, thoracic and mediastinal disorders Cough	6.7% 2/30 • Number of events 2 • Data was collected from week 0 to week 12 Does not differ	0.00% 0/16 • Data was collected from week 0 to week 12 Does not differ
Respiratory, thoracic and mediastinal disorders COVID-19	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	12.5% 2/16 • Number of events 2 • Data was collected from week 0 to week 12 Does not differ
Ear and labyrinth disorders Dizziness	13.3% 4/30 • Number of events 4 • Data was collected from week 0 to week 12 Does not differ	0.00% 0/16 • Data was collected from week 0 to week 12 Does not differ
Renal and urinary disorders Increase in Frequency of Urination	13.3% 4/30 • Number of events 4 • Data was collected from week 0 to week 12 Does not differ	0.00% 0/16 • Data was collected from week 0 to week 12 Does not differ
Gastrointestinal disorders Diarrhea	6.7% 2/30 • Number of events 2 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Endocrine disorders Fatigue	3.3% 1/30 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Skin and subcutaneous tissue disorders Poison Ivy	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 2 • Data was collected from week 0 to week 12 Does not differ
Skin and subcutaneous tissue disorders Hornet Sting	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Blood and lymphatic system disorders Worsening in Anemia	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Respiratory, thoracic and mediastinal disorders Sinus Infection	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Injury, poisoning and procedural complications Fall	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Cardiac disorders Chest Pain	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Musculoskeletal and connective tissue disorders Upper Leg Pain	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Gastrointestinal disorders Upset Stomach	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ
Musculoskeletal and connective tissue disorders Right Big Toe Pain	0.00% 0/30 • Data was collected from week 0 to week 12 Does not differ	6.2% 1/16 • Number of events 1 • Data was collected from week 0 to week 12 Does not differ