Clinical trial NCT04646902: Kynurenine/Tryptophan Ratio in Hypertension Associated to Obstructive Sleep Apnea
Official title: Relevance of the Ratio Kynurenine/Tryptophan to Characterize Hypertension Associated to Obstructive Sleep Apnea (KYNTOSA)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Hypertension Secondary
Keywords: hypertension
obstructive sleep apnea
tryptophan
aryl hydrocarbon receptor
Lead sponsor: Universidade Nova de Lisboa
Sponsor class: OTHER
Collaborators: name: Centro Hospitalar Lisboa Ocidental
name: Centro Hospitalar de Lisboa Central
name: Hospital Beatriz Ângelo
name: Hospital Fernando Fonseca
name: Hospital da Luz, Portugal
First posted: 2020-11-30
Enrollment: 203
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population will include 4 groups of adults: healthy volunteers; normotensive OSA patients; hypertensive OSA patients; hypertensive non OSA patients.

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.


Eligibility 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.

Primary outcomes:
measure: Kynurenine / Tryptophan ratio
timeFrame: Day 1 (visit 1)
Secondary outcomes:
measure: Concentrations of metabolites
timeFrame: Day 1 (visit 1)
Other outcomes:
Locations:
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Central
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental
city: Lisboa
country: Portugal
facility: Hospital Beatriz Ângelo
city: Lisboa
country: Portugal
facility: Hospital da Luz
city: Lisboa
country: Portugal
facility: Hospital Fernando Fonseca
Study officials:
affiliation: Universidade NOVA Lisboa
name: Maria E Monteiro, PhD
role: PRINCIPAL_INVESTIGATOR
References: