Vitamin D and SGLT-2 Inhibitor in CPAP-naive Obstructive Sleep Apnea

NCT06690723 | Completed Phase 3 DMC FDA Drug

• 3 other identifiers: UNIMAS_OSAFRGS/1/2021/SKK01/UNIMAS/02/1F05/IMPACT/2122/2021
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if vitamin D supplement and SGLT-2 inhibitor treatment combination can improve cardiovascular risks in patients with OSA and hypertension, on top of lifestyle modification, before treatment with CPAP therapy. It aims to answer if this treatment combination can improve i) renin-angiotensin-aldosterone system (RAAS) parameters, ii) cardio-metabolic risks iii) sleepiness symptoms and quality of life Researchers will compare the outcome with 3 other groups of treatment: vitamin D supplementation and lifestyle modification, SGLT2-inhibitor and lifestyle modification, and lifestyle modification alone. Participants will need to answer 2 questionnaires (Epworth Sleepiness Scale, WHO-quality of life), undergo anthropometric measurements (blood pressure, pulse rate, weight, height, waist circumference, neck circumference), blood taking (aldosterone, renin, vitamin D, calcium, albumin, phosphate, intact parathyroid hormone, kidney function, blood sugar, cholesterol and hsCRP), ultrasound of liver, ultrasound of blood vessel, and heart rate variability assessment using Polar H10 device and 24-hour Holter monitoring.

Conditions

Obstructive Sleep Apnea

Keywords

Obstructive sleep apnea; Hypertension; Vitamin D; Sodium glucose transporter-2 inhibitor; Dapagliflozin; Endothelial function; Metabolic dysfunction associated steatotic liver disease; MASLD; Heart rate variability; Cardiac autonomic function

Outcome Measures

Primary Outcomes (4)

• hsCRP (mg/L)

  To examine the effect of vitamin D supplement and SGLT2i treatment combination on improving hsCRP which reflect inflammation. The lower the hsCRP, the better the health outcomes

  16 weeks

• Endothelial function

  To determine the effect of combining vitamin D3 and SGLT2i treatment combination in improving endothelial function assessed via ultrasound flow-mediated dilatation of brachial artery, where normal is \>7.1%

  16 weeks

• Metabolic-associated steatotic liver disease

  To evaluate the effect of vitamin D3 and SGLT2i treatment combination in improving steatotic liver disease, which are graded as normal, grade 1, grade 2, and grade 3

  16 weeks

• Heart rate variability

  To evaluate the effect of vitamin D3 and SGLT2i treatment combination in improving heart rate variability (HRV) assessed via Polar H10 device (for short-term HRV) and 24-hour Holter monitoring (for long-term HRV).

  16 weeks

Secondary Outcomes (4)

• Plasma aldosterone levels (ng/dL)

  16 weeks

• Plasma renin levels (uIU/mL)

  16 weeks

• Sleepiness symptoms

  16 weeks

• Quality of life

  16 weeks

Study Arms (4)

Lifestyle modification

ACTIVE COMPARATOR

Participants are taught about lifestyle modification including diet and exercise

Behavioral: Lifestyle modification

Vitamin D3 (Cholecalciferol)

ACTIVE COMPARATOR

Participants are given vitamin D3 for 16 weeks on top of lifestyle modification advice

Drug: Vitamin D3 ( Colecalciferol)

Dapagliflozin (Forxiga)

ACTIVE COMPARATOR

Participants are given Dapagliflozin 10mg daily for 16 weeks on top of lifestyle modification advice

Drug: Dapagliflozin (Forxiga)

Vitamin D3 plus Dapagliflozin

ACTIVE COMPARATOR

Participants are given vitamin D3 plus Dapagliflozin 10mg daily for 16 weeks on top of lifestyle modification advice

Drug: Vitamin D3 plus Dapagliflozin

Interventions

Dapagliflozin (Forxiga) DRUG

Dapagliflozin plus lifestyle modification

Also known as: SGLT-2 inhibitor

Dapagliflozin (Forxiga)

Vitamin D3 ( Colecalciferol) DRUG

Vitamin D3 plus lifestyle modification

Vitamin D3 (Cholecalciferol)

Vitamin D3 plus Dapagliflozin DRUG

Vitamin D3 plus Dapagliflozin plus lifestyle modification

Vitamin D3 plus Dapagliflozin

Lifestyle modification BEHAVIORAL

Lifestyle modification alone

Lifestyle modification

Eligibility Criteria

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

You may qualify if:

• Aged 18 years and above
• Obstructive sleep apnea (OSA) confirmed on sleep study
• Hypertension (SBP\>140mmHg and/or DBP\>90mmHg) or on anti-hypertensive

You may not qualify if:

• Diagnosis of secondary hypertension
• Undergone surgical or medical therapy for PA
• Chronic kidney disease (eGFR\<30ml/min/1.73m2)
• Long term use of systemic steroids
• Presence of thyroid dysfunction or suspected Cushing's syndrome
• On current use of continuous positive airway pressure (CPAP) therapy for OSA
• Recent myocardial infarction or stroke (within 6 weeks prior to study)
• Congestive heart failure
• Long-standing atrial fibrillation, ie atrial fibrillation \>12 months in duration
• On vitamin D supplements
• On SGLT-2 inhibitor
• Underlying type 1 diabetes or history of ketoacidosis
• History of severe recurrent genito-urinary tract infections
• History of, or increased risk of, bone fractures
• Pregnant

Sponsors & Collaborators

• University Malaysia Sarawak: lead

Study Sites (1)

University Malaysia Sarawak

Sarawak, Sarawak, 94300, Malaysia

Location

Related Publications (1)

• Loh HH, Tay SP, Koa AJ, Yong MC, Said A, Chai CS, Abdul Malik NM, Su AT, Tang BBC, Tan FHS, Sukor N. Unveiling the benefits of Vitamin D3 with SGLT-2 inhibitors for hypertensive obese obstructive sleep apnea patients. J Transl Med. 2025 Mar 7;23(1):296. doi: 10.1186/s12967-025-06312-w.

  PMID: 40055713 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Hypertension

Interventions

dapagliflozin; Sodium-Glucose Transporter 2 Inhibitors; Cholecalciferol

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2024
• First Posted: November 15, 2024
• Study Start: June 8, 2022
• Primary Completion: September 3, 2024
• Study Completion: September 3, 2024
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)