Kynurenine/Tryptophan Ratio in Hypertension Associated to Obstructive Sleep Apnea (KYNTOSA)

New University of Lisbon

Status: Active, not recruiting

Conditions: Hypertension Secondary

Study type: Observational

Funder types: Other

Identifiers

NCT04646902

PTDC/MED-TOX30418/2017 (Other Grant/Funding Number)

Kyntosa_02_20200428

Details and patient eligibility

About

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.

Enrollment: 203 patients

Sex: All

Ages: 30+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

CASES (subjects with hypertension with and without OSA)

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.

Trial design

203 participants in 4 patient groups

HTN_OSA

Description:

Patients with hypertension\* with obstructive sleep apnea\*\* \* Hypertension will be defined as: i) use of antihypertensive drug(s) and stable dose for at least 2 weeks prior to inclusion; or ii) in untreated patients: office systolic blood pressure values \>= 140 mmHg and/ or diastolic blood pressure values \>= 90 mmHg. \*\* OSA will be defined with a polysomnography level 1, 2 or 3 performed within the previous twelve months with: * an apnea-hypopnea index \> 5 events per hour (with more than 50% of obstructive events) associated with symptoms (associated sleepiness, fatigue, insomnia, snoring, subjective nocturnal respiratory disturbance or observed apnea) or medical/psychiatric disorder (hypertension, coronary artery disease, atrial fibrillation, congestive heart failure, stroke, diabetes, cognitive dysfunction, or mood disorder), OR * an apnea-hypopnea index \> 15 events per hour, AND * no significant changes in health, medications, or lifestyle since the polysomnography.

HTN_NoOSA

Description:

Patients with hypertension without obstructive sleep apnea

NoHTN_OSA

Description:

Patients without hypertension with obstructive sleep apnea

NoHTN_NoOSA

Description:

Patients without hypertension without obstructive sleep apnea (healthy controls)