Kynurenine/Tryptophan Ratio in Hypertension Associated to Obstructive Sleep Apnea

Active, not recruiting

• Conditions: Hypertension Secondary

• Registration Number: NCT04646902
• Lead Sponsor: Universidade Nova de Lisboa

Brief Summary

Obstructive Sleep Apnea (OSA) is an independent risk factor for hypertension (HTN) and the most common cause of resistant HTN. The mechanisms underlying OSA-associated HTN are not completely understood. This is crucial to find novel therapeutic targets of OSA-associated HTN. The Aryl Hydrocarbon Receptor (AHR) is a cytosolic transcription factor that has been linked with the pathogenesis of HTN.

This study aims to evaluate the role of endogenous ligands of AHR such as kynurenine in discriminating patients with OSA-associated HTN. For that aim, a case-control study will be performed in patients with and without hypertension exposed and not exposed to OSA. Kynurenine and other metabolites will be quantified in urine and serum samples.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-10-12
• Study First Submitted QC: 2020-11-20
• Study First Posted: 2020-11-30
• Study Start: 2021-03-25
• Primary Completion: 2023-09-01
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-06
• Last Update Posted: 2023-12-07
• Study Completion: 2024-03-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 203

Inclusion Criteria

• Adults ≥ 30 years old attending the outpatient clinics of the clinical sites.
• Diagnosis of hypertension defined either as: a) use of antihypertensive drug(s) and stable dose for at least 2 weeks prior to inclusion; or b) in untreated patients: office systolic blood pressure values >= 140 mmHg and/ or diastolic blood pressure values >= 90 mmHg.
• Able to understand and communicate effectively with study personnel.
• Giving written informed consent to participate.

Exclusion Criteria

• Self-reported pregnancy or breastfeeding.
• Patients on haemodialysis or peritoneal dialysis.
• Chronic liver disease with Child-Pugh score B or higher.
• Hypertension attributed to renal artery stenosis, primary hyperaldosteronism, pheochromocytoma, Cushing's syndrome, coarctation of aorta.
• History of any OSA surgical treatment to the palatal and hypopharyngeal regions, notably uvulopalatopharyngoplasty surgery (UPPP), palatal radio frequency ablation, tonsillectomy, lingual tonsillectomy, partial glossectomy, tongue base radio frequency ablation, genioglossal advancement, hyoid suspension, maxillomandibular advancement surgery (MMA) and active use of hypoglossal nerve stimulator.
• Patients with a good adherence to CPAP, defined as the use of CPAP for at least 4 hours/night on 70% of nights during the last 3 months.
• Pulmonary hypertension.
• Current diagnosed oncological disease.
• Patients with known chronic or acute infectious diseases.
• Other current severe progressive or uncontrolled disease which in the judgement of the investigator renders the patient unsuitable for the study

CONTROLS (individuals without hypertension with and without OSA) For each case, an age and gender-matched control will be selected.

Exclusion Criteria:

• Pregnancy or breastfeeding.
• Patients on haemodialysis or peritoneal dialysis.
• Chronic liver disease with Child-Pugh score b or higher.
• History of any OSA surgical treatment to the palatal and hypopharyngeal regions, notably uvulopalatopharyngoplasty surgery (UPPP), palatal radio frequency ablation, tonsillectomy, lingual tonsillectomy, partial glossectomy, tongue base radio frequency ablation, genioglossal advancement, hyoid suspension, maxillomandibular advancement surgery (MMA) and active use of hypoglossal nerve stimulator.
• Patients with a good adherence to CPAP, defined as the use of CPAP for at least 4 hours/night on 70% of nights during the last 3 months.
• Pulmonary hypertension.
• Current diagnosed oncological disease.
• Patients with known chronic or acute infectious diseases.
• Patients with known chronic or acute infectious diseases.
• Other current severe progressive or uncontrolled disease which in the judgement of the investigator renders the patient unsuitable for the study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Kynurenine / Tryptophan ratio	Day 1 (visit 1)	Ratio between kynurenine and tryptophan concentrations

Secondary Outcome Measures

Name	Time	Method
Concentrations of metabolites	Day 1 (visit 1)	The relevant metabolites and their concentration will be identified by Partial Least Square Discriminant Analysis (PLS-DA) applied to non-targeted metabolomics.

Trial Locations

Locations (5)

Hospital Fernando Fonseca; 🇵🇹 Lisboa, Portugal

Hospital Beatriz Ângelo; 🇵🇹 Lisboa, Portugal

Centro Hospitalar de Lisboa Central; 🇵🇹 Lisboa, Portugal

Centro Hospitalar Lisboa Ocidental; 🇵🇹 Lisboa, Portugal

Hospital da Luz; 🇵🇹 Lisboa, Portugal