CPAP Effect on Lipid Profile and Hyperuricemia in Patients With Dyslipidemia and Moderate-severe Obstructive Sleep Apnea (CPAPLIP)

Effect of 12 Months of Treatment With Continuous Positive Airway Pressure on Lipid Profile and Hyperuricemia in Patients With Dyslipidemia and Moderate-severe Obstructive Sleep Apnea. A Randomized, Open-labell, Parallel Clinical Trial

Clinical Trial Phase IV Indication: Moderate-severe obstructive sleep apnea and dyslipidemia.

Objectives:

Main objective: To test whether 12 months of CPAP treatment associated with conventional pharmacological treatment improves the lipid profile of patients with dyslipidemia and moderate to severe OSA.

Secondary objectives:

• To test whether 12 months of treatment with CPAP associated with conventional pharmacological treatment improves serum uric acid concentration in patients with dyslipidemia and moderate-severe OSA.
• To determine the additional medium- and long-term effect of CPAP on insulin resistance in patients with dyslipidemia and moderate-severe OSA.
• To evaluate the impact of CPAP treatment on cardiovascular risk reduction in patients with dyslipidemia and moderate-severe OSA.
• To analyze the impact of supplemental CPAP treatment on glycemic control and C-reactive protein concentration in patients with dyslipidemia and moderate-severe OSA.
• To establish the impact of supplemental CPAP therapy on health-related quality of life in patients with dyslipidemia and moderate-severe OSA.
• To evaluate the effect of CPAP on inflammatory cytokines, oxidative stress biomarkers, sympathetic tone and intake-regulating hormones in patients with dyslipidemia and moderate-severe OSA.
• To relate CPAP-induced changes in serum lipid and uric acid concentration to changes in basal inflammatory response, oxidative stress, sympathetic activity, and intake-regulating hormones.
• To identify the subgroup of patients with dyslipidemia and moderate-severe OSA in whom 12 months of CPAP treatment achieves a more marked reduction in serum lipids and uric acid.

Design Randomized, parallel-group, nonblinded, controlled clinical trial with conventional treatment.

Study population Subjects aged 35 to 80 years with a diagnosis of dyslipidemia made at least six months ago and with moderate-severe obstructive sleep apnea (OSA) not requiring CPAP treatment according to conventional indications.

Sample size: 110 patients in each treatment arm.

Treatment Patients will be randomly assigned in a 1:1 ratio to one of the following treatment arms:

1. Conventional hygienic-dietary recommendations and promotion of daily physical activity.
2. Conventional hygienic-dietary recommendations and promotion of daily physical activity, plus treatment with positive airway pressure (CPAP).

Efficiency variables

• Main variables: LDL-cholesterol and uric acid.
• Total cholesterol, HDL-cholesterol and triglycerides.
• Basal blood glucose, glycosylated hemoglobin (HbA1c), creatinine and C-reactive protein.
• Systemic biomarkers: inflammatory (IL-6, IL-8 and TNF-α), oxidative stress (8-isoprostane), endothelial damage (endothelin, VCAM-1 and ICAM-1), sympathetic activity (neuropeptide Y) and appetite-regulating hormones (leptin, orexin A/hypocretin 1 and ghrelin).
• Clinical questionnaires: SF-12, EuroQoL, FOSQ and IPAQ.

Safety variables

• Clinical adverse event reporting.
• CPAP compliance (average hours of use per day).
• Epworth Sleepiness Questionnaire.
• Development of cardiovascular events.

Study Overview

• Status: Recruiting
• Conditions: Dyslipidemias; Sleep Apnea; Hyperuricemia
• Intervention / Treatment: Other: Hygienic-dietary recommendations and daily physical activity promotion; Device: Continuous positive airway pressure

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Francisco Garcia-Rio, MD; Phone Number: +34639911718; Email: fgr01m@gmail.com
• Study Contact Backup: Name: Francisco Garcia-Rio; Phone Number: +34639911718; Email: fgr01m@gmail.com

Study Locations

• Spain
  • Madrid
    • Coslada, Madrid, Spain, 28822
      • Recruiting
      • Hospital Universitario del Henares
      • Contact: Angeles Ruiz-Cobos, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects from 35 to 80 years old
• Diagnosis of dyslipidemia. It will be considered as such, the existence of a previous clinical record of a diagnosis of dyslipidemia associated with treatment with lipidlowering agents, treatment with lipid-lowering agents or the presence of an altered blood test in the last two months, using the following cut-off points: total cholesterol ≥ 200 mg/dl, triglycerides ≥ 180 mg/dl, HDL-cholesterol ≤ 40 mg/dl or LDL-cholesterol ≥ 150 mg/dl.
• Moderate-severe sleep apnea, defined by AHI > 15 h-1 .

Exclusion Criteria:

• Predominance of central apneas-hypopneas, defined as more than 25% of total respiratory events.
• Patients with indications for CPAP treatment according to the International Sleep Consensus: hypertensive, excessive daytime sleepiness (Epworth Sleepiness Scale > 11) or impaired sleep-related quality of life considered relevant by their regular physician.
• Professional drivers, at-risk profession or respiratory insufficiency (according to criteria of the clinical pathway for the diagnosis and treatment of sleep-disordered breathing).
• Pretreatment with CPAP

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group; Conventional hygienic-dietary recommendations and promotion of daily physical activity	Other: Hygienic-dietary recommendations and daily physical activity promotion; Hygienic-dietary recommendations on sleep and intervention for the promotion of daily physical activity, establishing walking as a goal 10,000 steps per day. To do this, they will be provided with a pedometer and asked to fill out a form with the steps walked each day. At each visit, the distance walked will be reviewed and the goal set will be reiterated.
Experimental: CPAP group; Conventional hygienic-dietary recommendations and promotion of daily physical activity, plus treatment with positive airway pressure (CPAP)	Other: Hygienic-dietary recommendations and daily physical activity promotion; Hygienic-dietary recommendations on sleep and intervention for the promotion of daily physical activity, establishing walking as a goal 10,000 steps per day. To do this, they will be provided with a pedometer and asked to fill out a form with the steps walked each day. At each visit, the distance walked will be reviewed and the goal set will be reiterated.; Device: Continuous positive airway pressure; Treatment will start with an empirical pressure of 8 cmH2O and, within a maximum of 3 weeks, the pressure will be adjusted by means of automatic titration, establishing the pressure corresponding to the 95th percentile.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CPAP effect on lipid profile	Comparison of 12-months change from baseline in the plasma level of LDL-cholesterol between the two study groups	12 months
CPAP effect on lipid profile-2	Comparison of 12-months change from baseline in the plasma level of HDL-cholesterol between the two study groups	12 months
CPAP effect on lipid profile-3	Comparison of 12-months change from baseline in the plasma level of total cholesterol between the two study groups	12 months
CPAP effect on lipid profile-4	Comparison of 12-months change from baseline in the plasma level of triglycerides between the two study groups	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CPAP effect on uric acid	Comparison of 12-months change from baseline in the plasma level of uric acid between the two study groups	12 months
Medium-term CPAP effect on insulin resistance	Comparison of 6-months change from baseline in the HOMA index between the two study groups	6 months
Long-term CPAP effect on insulin resistance	Comparison of 12-months change from baseline in the HOMA index between the two study groups	12 months
CPAP effect on cardiovascular risk	Comparison of 12-months change from baseline in the cardiovascular risk score between the two study groups	12 months
CPAP effect on glycemic control	Comparison of 12-months change from baseline in the plasma level of HbA1c between the two study groups	12 months
CPAP effect on C-reactive protein	Comparison of 12-months change from baseline in the plasma level of C-reactive protein between the two study groups	12 months
CPAP effect on sleepiness	Comparison of 12-months change from baseline in the Epworth sleepiness scale between the two study groups	12 months
CPAP effect on health-related quality of life	Comparison of 12-months change from baseline in the EuroQoL score between the two study groups	12 months
CPAP effect on health-related quality of life-2	Comparison of 12-months change from baseline in the SF-12 score between the two study groups	12 months
CPAP effect on daily physical activity	Comparison of 12-months change from baseline in the iPAQ score between the two study groups	12 months
CPAP effect on inflammatory cytokines	Comparison of 12-months change from baseline in the plasma levels of IL-6, IL-8 and TNF-α between the two study groups	12 months
CPAP effect on oxidative stress biomarkers	Comparison of 12-months change from baseline in the plasma level of 8-isoprostane between the two study groups	12 months
CPAP effect on sympathetic tone	Comparison of 12-months change from baseline in the plasma level of neuropeptide Y between the two study groups	12 months
CPAP effect on intake-regulating hormones	Comparison of 12-months change from baseline in the plasma levels of leptin, orexin A/hypocretin 1 and ghrelin between the two study groups	12 months

Collaborators and Investigators

• Sponsor: Hospital Universitario La Paz
• Collaborators: Hospital Universitario del Henares
• Investigators: Study Chair: Maria Angeles Ruiz-Cobos, MD, Hospital Universitario del Henares; Principal Investigator: Ana De la Rocha Prieto, MD, Hospital Universitario del Henares; Principal Investigator: Julia Dorta Díez de la Lastra, MD, Hospital Universitario del Henares; Principal Investigator: Raquel Casitas, MD, Hospital Universitario La Paz; Principal Investigator: Marina Blanco Cruz, ND, Hospital Universitario del Henares

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2024
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: June 12, 2024
• First Submitted That Met QC Criteria: June 14, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): July 15, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Lipid Metabolism Disorders; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Dyslipidemias; Hyperuricemia
• Other Study ID Numbers: 082024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No