Dapagliflozin Effect in Cognitive Impairment in Stroke Trial

Metabolic Syndrome Clinical Trial

— DECIST  

Official title:

Dapagliflozin Effect in Cognitive Impairment in Stroke Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05565976
• Other study ID #: F-2022-1005-016
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 1, 2020
• Est. completion date: July 1, 2025

Study information

• Verified date: October 2022
• Source: Universidad de Guanajuato
• Contact: Omar Jiménez-Zarazúa, M.D.
• Phone: +524423421626
• Email: drzarazuainterna[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background: Dementia is an international public health problem, affecting approximately 50,000,000 people worldwide in 2018 and will triple by 2050; furthermore, reaching an approximate cost of 4 billion dollars. Given its high worldwide prevalence and probable underdiagnosis, the international guidelines for the assessment of dementia syndromes recommend the assessment of cognitive impairment in patients over 55 years of age as part of clinical practice in patients who presented an ischemic cerebrovascular event. Several risk factors associated with cognitive impairment in cerebrovascular disease are identified in the literature: 1) demographic factors (e.g., age over 65 years and female sex); 2) risk factors present prior to the ischemic stroke (e.g., cognitive impairment, physical impairment); 3) factors utilized to assess the severity of an ischemic stroke (e.g., supratentorial location, ischemic stroke in the dominant hemisphere, recurrence of ischemic strokes); 4) post-ischemic stroke factors (e.g., delirium and seizures); and 5) factors associated with neuroimaging findings (e.g., cerebral small vessel disease, cortical atrophy, and medial temporal lobe atrophy). This is a randomized controlled trial in individuals with an acute ischemic stroke without dementia that will be treated with 10mg dapagliflozin PO q24h for 12 months and standard treatment against only standard treatment (i.e., statins, platelet antiaggregant, and hypoglycemic medications) when appropriate. The outcome measure evaluated will be global cognitive function. Cardiovascular risk factors will be associated with cognitive decline.

Description:

Detailed Description: This is a double-blind, randomized, placebo-controlled, parallel-group, 12-month longitudinal study performed at a single center (Hospital General de Zona con Medicina Familiar IMSS No. 21, León Guanajuato, México) designed to investigate the effect of dapagliflozin in participants with a recent acute stroke but no history of dementia (CDR score ≤ 0.5). A total of 270 participants are to be included (i.e., 135 on each arm). Overall objective: To assess the effect of Dapagliflozin on cardiovascular risk (i.e., the volume of epicardial fat, volume of total carotid atherosclerotic plaque, and coronary artery calcium score) in patients with ischemic cerebrovascular disease dependent on global cognitive function at a second level teaching hospital in Mexico. Statistical analysis: Descriptive statistics will be reported for all included variables. Statistical analysis will be performed using SPSS 25 (SPSS Inc., Chicago, IL). All variables will be examined to determine the existence of outliers and whether they meet the assumptions about a Gaussian distribution. The Shapiro-Wilk tests will be used to determine normality distribution, as well as visual inspection of histograms and Q-Q plots. Demographic and clinical variables will be summarized in proportions and percentages. The categorical variables will be evaluated to determine statistical inferences with the Mann-Whitney U test. Continuous variables will be assessed for statistical inferences using t-tests (e.g., simple, paired, one, and two samples) and Levene's test to assess equality of variances. The Kaplan-Meier method will be used to calculate the distributions of mortality and development of mild amnestic cognitive disorder and dementia syndrome. The Gehan-Breslow-Wilcoxon method will be used to assess the equality of the mortality distributions and the development of mild amnestic cognitive disorder or dementia syndrome. A multivariate analysis will be performed with a Cox regression model to assess the variables that predict mortality, and the development of a mild amnestic cognitive disorder, or dementia syndrome at 6 and 12 months in case there are differences in mortality distributions. Statistical significance will be set at p=0.05 and a Bonferroni correction will be performed for multiple comparisons.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: July 1, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

Inclusion Criteria:

• Ages of 60 and 80 years
• Both sexes
• Cerebrovascular ischemic event within 15 days
• Clinical dementia rating score = 0.5
• Signed informed consent

Exclusion Criteria:

• Type 1 diabetes mellitus
• Aphasia
• Incomplete neuropsychological battery
• Previously diagnosed dementia
• Cerebrovascular ischemic stroke older than 15 days
• History of hemorrhagic cerebrovascular event
• Neoplasia diagnosis or evidence of a metastatic process, glomerular filtration rate < 45 mL/min at the time of inclusion
• Liver enzyme test alterations (i.e., aspartate transaminase or alanine transaminase three times greater than normal levels, total bilirubin> 2.0 mg/dL
• Previously taking SGLT2 inhibitors
• History of diabetic ketoacidosis
• Recurrent urinary tract infections
• Psychiatric disorders (e.g., dementia, psychosis, bipolar disorder, among others).
• Less than a 12-month follow-up
• Inability to perform chest CT (e.g., claustrophobia)
• Incomplete medical files pertaining to the variables of interest
• Less than 12-month follow-up
• Decision to withdraw their participation at any moment
• Poor adherence to medical treatment
• Reported and documented disease complications or adverse effects (e.g., severe glycemic imbalance, diabetic ketoacidosis, or hyperosmolar hyperglycemic state, altered hepatic enzyme tests)

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Dementia, Vascular
• Ischemic Stroke
• Metabolic Syndrome
• Mild Cognitive Impairment
• Stroke
• Stroke, Ischemic

Intervention

Drug:
• Dapagliflozin 10mg Tab
10mg PO q24h for 12 months
• Statins (Cardiovascular Agents)
Atorvastatin 20mg PO q24h or Pravastatin 20mg PO q24h or Rosuvastatin 10mg PO q24h
• Platelet Antiaggregant
Clopidogrel 75mg PO q24h or Acetylsalicylic acid 100mg PO q24h
• Antidiabetic
Previously established medical treatment for type 2 diabetes will be maintained.

Locations

Country	Name	City	State
Mexico	Hospital General de Zona IMSS 21	León	Guanajuato

Sponsors (4)

Lead Sponsor	Collaborator
Jaime Daniel Mondragon	Hospital General de Zona IMSS N0. 21, Hospital General León, University Medical Center Groningen

Country where clinical trial is conducted

Mexico, 

References & Publications (22)

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Sato T, Aizawa Y, Yuasa S, Fujita S, Ikeda Y, Okabe M. The Effect of Dapagliflozin Treatment on Epicardial Adipose Tissue Volume and P-Wave Indices: An Ad-hoc Analysis of The Previous Randomized Clinical Trial. J Atheroscler Thromb. 2020 Dec 1;27(12):1348 — View Citation

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Zlokovic BV, Gottesman RF, Bernstein KE, Seshadri S, McKee A, Snyder H, Greenberg SM, Yaffe K, Schaffer CB, Yuan C, Hughes TM, Daemen MJ, Williamson JD, González HM, Schneider J, Wellington CL, Katusic ZS, Stoeckel L, Koenig JI, Corriveau RA, Fine L, Gali — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse effects due to Dapagliflozin	Adverse effects reported due to the use of dapagliflozin	12 months
Primary	Change in Clinical Dementia Rating score as a proxy of cognitive deterioration	Time-to-event analysis using the Kaplan-meier survival analysis via increase in Clinical Dementia Rating score greter or equal to 0.5	6 and 12 months
Secondary	Number of strokes after initial cerebrovascular event	Independent stroke events	12 months