Dapagliflozin Effect in Cognitive Impairment in Stroke Trial

NCT ID: NCT05565976

Last Updated: 2022-10-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 270 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-01
• Study Completion Date: 2025-07-01

Brief 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.

Detailed 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.

Conditions

Stroke, Ischemic; Mild Cognitive Impairment; Dementia, Vascular; Metabolic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Dapagliflozin

10mg PO q24h for 12 months plus standard treatment with statins, platelet antiaggregant, and hypoglycemic medications.

Group Type: EXPERIMENTAL

Dapagliflozin 10mg Tab

Intervention Type: DRUG

10mg PO q24h for 12 months

Statins (Cardiovascular Agents)

Intervention Type: DRUG

Atorvastatin 20mg PO q24h or Pravastatin 20mg PO q24h or Rosuvastatin 10mg PO q24h

Platelet Antiaggregant

Intervention Type: DRUG

Clopidogrel 75mg PO q24h or Acetylsalicylic acid 100mg PO q24h

Antidiabetic

Intervention Type: DRUG

Previously established medical treatment for type 2 diabetes will be maintained.

Standard treatment

Standard treatment with statins, platelet antiaggregant, and hypoglycemic medications.

Group Type: ACTIVE_COMPARATOR

Statins (Cardiovascular Agents)

Intervention Type: DRUG

Atorvastatin 20mg PO q24h or Pravastatin 20mg PO q24h or Rosuvastatin 10mg PO q24h

Platelet Antiaggregant

Intervention Type: DRUG

Clopidogrel 75mg PO q24h or Acetylsalicylic acid 100mg PO q24h

Antidiabetic

Intervention Type: DRUG

Previously established medical treatment for type 2 diabetes will be maintained.

Interventions

Dapagliflozin 10mg Tab

10mg PO q24h for 12 months

Intervention Type: DRUG

Statins (Cardiovascular Agents)

Atorvastatin 20mg PO q24h or Pravastatin 20mg PO q24h or Rosuvastatin 10mg PO q24h

Intervention Type: DRUG

Platelet Antiaggregant

Clopidogrel 75mg PO q24h or Acetylsalicylic acid 100mg PO q24h

Intervention Type: DRUG

Antidiabetic

Previously established medical treatment for type 2 diabetes will be maintained.

Intervention Type: DRUG

Other Intervention Names

FORXIGA; Atorvastatin; Pravastatin; Rosuvastatin; Clopidogrel; Acetylsalicylic acid; Sulfonylureas; Meglitinides; Biguanides; Thiazolidinediones; α-Glucosidase inhibitors; Inhibitors of dipeptidyl peptidase 4; Cycloset; Insulin glargine; Insulin lispro; Isophane insulin

Eligibility Criteria

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)

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital General León

UNKNOWN

Sponsor Role: collaborator

Hospital General de Zona IMSS N0. 21

UNKNOWN

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

Jaime Daniel Mondragon

OTHER

Sponsor Role: lead

Responsible Party

Jaime Daniel Mondragon

Principal Investigator, Clinical Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Gabriela G López-Hernández, M.D.

Role: STUDY_CHAIR

Hospital General de Zona IMSS 21

Lizeth C Ramírez-Zamudio, M.D.

Role: STUDY_CHAIR

Hospital General de Zona IMSS 21

Jaime D Mondragón, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen, Department of Neurology, Alzheimer Center Groningen

Locations

Hospital General de Zona IMSS 21

León, Guanajuato, Mexico

Site Status: RECRUITING

Countries

Mexico

Central Contacts

Omar Jiménez-Zarazúa, M.D.

Role: CONTACT

drzarazuainterna@hotmail.com

+524423421626

Lourdes N Vélez-Ramírez, M.D.

Role: CONTACT

nestlynoemi@gmail.com

Facility Contacts

Omar Jiménez-Zarazúa, M.D.

Role: primary

drzarazuainterna@hotmail.com

+524423421626

Gabriela G López-Hernández, M.D.

Role: backup

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Other Identifiers

F-2022-1005-016

Identifier Type: -

Identifier Source: org_study_id