Novel Inhibitors of Lipolysis in the Treatment of Lipid a Glucose Metabolism in Obstructive Sleep Apnea Syndrome

NCT05245240 | Unknown

• 1 other identifier: NU21-01-00259
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Obstructive sleep apnea syndrome (OSA) represents highly prevalent (typically overlooked, undiagnosed and untreated) disorder significantly increasing cardiovascular, cancer and overall mortality as well as increasing the risk of Type 2 diabetes and liver steatohepatitis. Unfortunately, adherence to state-of-the-art therapy with continuous positive airway pressure devices (CPAP) is poorly tolerated by patients, rendering a significant proportion (\~60-70 %) of them at undiminished cardiovascular and metabolic risk warranting development of innovative, pharmacological, treatment options. The overarching theme of this project is that metabolic impairments associated with OSA (e.g. Type 2 diabetes mellitus and non-alcoholic steatohepatitis) are causally mediated by elevated levels of circulating free fatty acids (FFA) originating from hypoxia-induced adipose tissue lipolysis. Increased plasma FFA subsequently induce insulin resistance, β-cell dysfunction, increase hepatic glucose output and stimulate lipid storage in liver. The investigators recently proved that hypoxia represents a powerful stimulus for adipocyte lipolysis and that experimental pharmacological inhibition of lipolysis prevented development of Type 2 diabetes in a mouse model of OSA. The goal of the project is to understand adipose tissue lipolysis derangements in OSA subjects and to evaluate the feasibility of lifestyle intervention as a mean to reduce spontaneous lipolysis.

Conditions

Obstructive Sleep Apnea; Obesity

Outcome Measures

Primary Outcomes (1)

• Glycerol release (lipolysis) in adipose tissue measured by microdialysis

  Changes in interstitial glycerol concentration in adipose tissue before and after exercise and dietary intervention

  Baseline and 6 months

Secondary Outcomes (1)

• Weight loss measurements

  6 months

Study Arms (2)

Severe OSA group

EXPERIMENTAL

Dietary and physical activity intervention

Procedure: Dietary and physical intervention

Mild OSA group

EXPERIMENTAL

Dietary and physical activity intervention

Procedure: Dietary and physical intervention

Interventions

Dietary and physical intervention PROCEDURE

Low-caloric diet (energy deficit 600 kcal/day based on indirect calorimetry measurements), individually tailored by a nutritional specialist according to patients' individual food preferences. Mild to moderate intensity exercise of aerobic/endurance type, performed 3 times a week for 30-90 minutes.

Mild OSA group; Severe OSA group

Eligibility Criteria

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

You may qualify if:

• mild (AHI \< 10) or severe (AHI \> 30) OSA diagnosed by home sleep study
• BMI 30-40 kg/m2
• age 18 - 65 years
• absence of diabetes mellitus (fasting glucose level \< 7 mmol/l, HBA1c \< 48 mmol/l and oGTT \< 11.1 mmol/L 2 hours after 75g oral glucose load)
• no treatment with drugs affecting lipolysis (betablockers, alpha adrenergic blockers, glucocorticoids).

You may not qualify if:

• cardiac, renal or respiratory; chronic inflammatory or cancer disease
• body weight change more than 5 kg in last 3 months
• inability to participate in the life-style program
• inability to give an informed consent
• participation in another research project
• pregnancy or planned pregnancy during the study period

Sponsors & Collaborators

• Faculty Hospital Kralovske Vinohrady: lead

Study Sites (1)

University Hospital Královské Vinohrady

Prague, 100 34, Czechia

RECRUITING

MeSH Terms

Conditions

Sleep Apnea, Obstructive; Obesity

Interventions

Diet

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Jan Polak, MD, PhD

  Vascular surgery, University hospital Královské Vinohrady, Prague

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan Polak, MD, PhD

CONTACT

+420267162710; jan.polak@lf3.cuni.cz

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 3, 2022
• First Posted: February 17, 2022
• Study Start: January 1, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: February 17, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)