SGLT2-Inhibitors for Sleep Apnea in Heart Failure

• ClinicalTrials.gov Identifier: NCT04640493
• Recruitment Status: Not yet recruiting
• First Posted: November 23, 2020
• Last Update Posted: November 23, 2020
• Sponsor: Columbia University
• Information provided by (Responsible Party): Nir Uriel, Columbia University

Study Description

Brief Summary:

Heart Failure is a disease involving many different aspects of the human body, including changes in metabolism, the way the body produces and uses energy. Research shows that patients with heart failure often have a sleep disorder called sleep disordered breathing (SDB). It has been shown that SDB is associated with poor outcomes in heart failure patients, but the exact reason is unknown. It is likely that SDB leads to changes in metabolism and hormone status in the body, which is especially dangerous for heart failure patients. There is currently no treatment for SDB in heart failure patients. Recently, with Sodium glucose co-transporter 2 (SGLT2)-Inhibitors a new drug class has been approved for the treatment of advanced heart failure. This drug has effects on the metabolism in heart failure patients, among several other effects. This research project has the aim to investigate if SGLT2 inhibitors can help in the treatment of SDB, as many mechanisms of the drug overlap with the mechanisms how SDB develops. The drug has been approved by the FDA for the treatment of heart failure. The investigators want to study the effect of the drug on SDB by using a home sleep test called Watchpat, which has been approved to diagnose SDB.

Condition or disease	Intervention/treatment	Phase
Heart Failure; Sleep Disordered Breathing	Drug: Dapagliflozin; Device: WatchPat	Phase 2

Detailed Description:

To explore whether SGLT2-Inhibition has a beneficial effect on Sleep Disordered Breathing (SDB) in advanced heart failure patients. This project proposes to carry out research that addresses the established, but in clinical practice under-recognized association between Sleep Disordered Breathing (SDB) and a worse prognosis in patients with heart failure (HF). SDB is highly prevalent in the HF population. Multiple studies have shown that HF accompanied by SDB is associated with an increased mortality compared to the absence of SDB. Two major types of SDB are prevalent in HF: Obstructive Sleep Apnea (OSA) and Central Sleep Apnea (CSA). Mechanistically, it has been proposed that SDB impacts the neurohumoral axis and systemic metabolism and therefore has particularly detrimental effects on the HF patient population. Therapeutic options for the treatment of SDB are limited. Heart Failure is a multisystemic disease leading to maladaptive cardiac and systemic metabolic changes. Recently, with SGLT2-Inhibitors a new drug class has been approved for the treatment of advanced heart failure. This is the first drug class in the HF drug armamentarium targeting cardiometabolic mechanisms. This study seeks to improve the health of individuals with heart failure by exploring whether SGLT2-Inhibition has a beneficial effect on SDB (OSA and CSA) in advanced heart failure patients and therefore may be a novel therapeutic option for the treatment of SDB in advanced HF. The specific aim of this project is to assess the effect of therapy with a SGLT2-I on SDB in ambulatory advanced HF patients by using the WatchPAT-derived apnea-hypopnea index as well as subjective measures of sleep quality using the Berlin Questionnaire and Epworth Sleepiness Scale.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Study design is prospective, non-randomized, interventional (non-experimental) pre-post study
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: The Effect of Sodium Glucose Co-transporter 2 (SGLT2)-Inhibitors on Sleep Disordered Breathing in Heart Failure Patients
• Estimated Study Start Date: December 2020
• Estimated Primary Completion Date: July 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: SLGT2-SDB; Patients with newly diagnosed SDB will be given dapagliflozin (standard dosage, 10mg)	Drug: Dapagliflozin; If patients have been diagnosed with SDB using the WatchPat device, they will start dapagliflozin. Repeat WatchPat SDB assessment will be performed after 3 and 6 months of continuous dapagliflozin therapy.; Other Name: FARXIGA; Device: WatchPat; HF patients undergo SDB testing with the WatchPat device.

Outcome Measures

Primary Outcome Measures :

1. Change in Apnea-Hypopnea Index [ Time Frame: 6 months ]
   Change in the apnea-hypopnea index as measured by the WatchPAT device.
2. Change Berlin Questionnaire Categorization [ Time Frame: 6 months ]
   The Berlin Questionnaire for sleep apnea consists of 3 categories related to the risk of having sleep apnea. Participants are classified as "High Risk" or "Low Risk" for sleep apnea. High risk categorization is assigned when there are 2 or more categories where the score is positive ("positive" defined as a score of 2 or more points). Low risk categorization is assigned when there is 1 or no categories where the score is positive.
3. Change in Epworth Sleepiness Scale [ Time Frame: 6 months ]
   The Epworth Sleepiness Scale is an 8-item scale measuring sleepiness in various situations. Each situation is scored as 0=no chance of dozing to 3= high chance of dosing. Scores range from 0-24, with a higher score indicating a higher level of sleepiness.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Consent-able adults
• Diagnosis of heart failure
• Diagnosis of SDB
• No contraindication for taking dapagliflozin

Exclusion Criteria:

• Patients without heart failure
• Patients without SDB
• Contraindication for taking dapagliflozin (severe renal impairment, hemodialysis, or history of severe hypoglycemic episodes)

Contacts and Locations

Contacts

Contact: Nir Uriel, MD; (212) 342-3259; nu2126@cumc.columbia.edu

Locations

United States, New York

Vivian and Seymour Milstein Family Heart Center

New York, New York, United States, 10032

Contact: Nir Uriel, MD

Principal Investigator: Nir Uriel, MD

Sponsors and Collaborators

Columbia University

Investigators

• Principal Investigator: Nir Uriel, MD; Columbia University

More Information

• Responsible Party: Nir Uriel, Professor of Medicine Columbia University Vagelos College of Physicians, Columbia University
• ClinicalTrials.gov Identifier: NCT04640493
• Other Study ID Numbers: AAAT2147
• First Posted: November 23, 2020
• Last Update Posted: November 23, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Nir Uriel, Columbia University:

heart failure; sleep disordered breathing; sglt2-inhibitor; sglt2; dapagliflozin; watchpat

Additional relevant MeSH terms:

Respiratory Aspiration; Sleep Apnea Syndromes; Heart Failure; Heart Diseases; Cardiovascular Diseases; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Dapagliflozin; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Physiological Effects of Drugs