Dapagliflozin Effect in Cognitive Impairment in Stroke Trial

NCT05565976 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: F-2022-1005-016
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

dapagliflozin; mortality; cognitive impairment

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Number of strokes after initial cerebrovascular event

  12 months

Other Outcomes (1)

• Adverse effects due to Dapagliflozin

  12 months

Study Arms (2)

Dapagliflozin

EXPERIMENTAL

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

Drug: Dapagliflozin 10mg Tab; Drug: Statins (Cardiovascular Agents); Drug: Platelet Antiaggregant; Drug: Antidiabetic

Standard treatment

ACTIVE COMPARATOR

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

Drug: Statins (Cardiovascular Agents); Drug: Platelet Antiaggregant; Drug: Antidiabetic

Interventions

Dapagliflozin 10mg Tab DRUG

10mg PO q24h for 12 months

Also known as: FORXIGA

Dapagliflozin

Statins (Cardiovascular Agents) DRUG

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

Also known as: Atorvastatin, Pravastatin, Rosuvastatin

Dapagliflozin; Standard treatment

Platelet Antiaggregant DRUG

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

Also known as: Clopidogrel, Acetylsalicylic acid

Dapagliflozin; Standard treatment

Antidiabetic DRUG

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

Also known as: Sulfonylureas, Meglitinides, Biguanides, Thiazolidinediones, α-Glucosidase inhibitors, Inhibitors of dipeptidyl peptidase 4, Cycloset, Insulin glargine, Insulin lispro, Isophane insulin

Dapagliflozin; Standard treatment

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Type 1 diabetes mellitus
• Aphasia
• Incomplete neuropsychological battery
• Previously diagnosed dementia
• Cerebrovascular ischemic stroke older than 15 days
• History of hemorrhagic cerebrovascular event
• 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

Sponsors & Collaborators

• Jaime Daniel Mondragon: lead
• Hospital General León: collaborator
• Hospital General de Zona IMSS N0. 21: collaborator
• University Medical Center Groningen: collaborator

Study Sites (1)

Hospital General de Zona IMSS 21

León, Guanajuato, 37380, Mexico

RECRUITING

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MeSH Terms

Conditions

Ischemic Stroke; Cognitive Dysfunction; Dementia, Vascular; Metabolic Syndrome

Interventions

dapagliflozin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Agents; Atorvastatin; Pravastatin; Rosuvastatin Calcium; Platelet Aggregation Inhibitors; Clopidogrel; Aspirin; Hypoglycemic Agents; Sulfonylurea Compounds; meglitinide; Biguanides; Thiazolidinediones; Bromocriptine; Insulin Glargine; Insulin Lispro; Insulin, Isophane

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Dementia; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Sulfones; Sulfur Compounds; Pyrimidines; Hematologic Agents; Ticlopidine; Thienopyridines; Thiophenes; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Physiological Effects of Drugs; Urea; Guanidines; Amidines; Thiazoles; Ergotamines; Ergot Alkaloids; Alkaloids; Ergolines; Heterocyclic Compounds, 4 or More Rings; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Short-Acting

Study Officials

• Gabriela G López-Hernández, M.D.

  Hospital General de Zona IMSS 21

  STUDY CHAIR

• Lizeth C Ramírez-Zamudio, M.D.

  Hospital General de Zona IMSS 21

  STUDY CHAIR

• Jaime D Mondragón, M.D., Ph.D.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Omar Jiménez-Zarazúa, M.D.

CONTACT

+524423421626; drzarazuainterna@hotmail.com

Lourdes N Vélez-Ramírez, M.D.

CONTACT

nestlynoemi@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Duoble-blinded study, only outcome assessor will have knowledge of labels.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, Clinical Professor

Study Record Dates

• First Submitted: September 20, 2022
• First Posted: October 4, 2022
• Study Start: August 1, 2020
• Primary Completion: December 31, 2024
• Study Completion: July 1, 2025
• Last Updated: October 4, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Starting august 2022
• Access Criteria: Request IMSS institutional board

Locations

ME (1)