Kynurenine/Tryptophan Ratio in Hypertension Associated to Obstructive Sleep Apnea

NCT04646902 | Unknown

• 2 other identifiers: Kyntosa_02_20200428PTDC/MED-TOX30418/2017
• Study Type: observational
• Target: 203
• Locations: 1 country
• Sites: 5

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.

Conditions

Hypertension Secondary

Keywords

hypertension; obstructive sleep apnea; tryptophan; aryl hydrocarbon receptor

Outcome Measures

Primary Outcomes (1)

• Kynurenine / Tryptophan ratio

  Ratio between kynurenine and tryptophan concentrations

  Day 1 (visit 1)

Secondary Outcomes (1)

• Concentrations of metabolites

  Day 1 (visit 1)

Study Arms (4)

HTN_OSA

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

Patients with hypertension without obstructive sleep apnea

NoHTN_OSA

Patients without hypertension with obstructive sleep apnea

NoHTN_NoOSA

Patients without hypertension without obstructive sleep apnea (healthy controls)

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Adults ≥ 30 years old attending the outpatient clinics of the clinical sites.
• Able to understand and communicate effectively with study personnel.
• Giving written informed consent to participate.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Universidade Nova de Lisboa: lead
• Centro Hospitalar Lisboa Ocidental: collaborator
• Centro Hospitalar de Lisboa Central: collaborator
• Hospital Beatriz Ângelo: collaborator
• Hospital Fernando Fonseca: collaborator
• Hospital da Luz, Portugal: collaborator

Study Sites (5)

Centro Hospitalar de Lisboa Central

Lisbon, Portugal

Location

Centro Hospitalar Lisboa Ocidental

Lisbon, Portugal

Location

Hospital Beatriz Ângelo

Lisbon, Portugal

Location

Hospital da Luz

Lisbon, Portugal

Location

Hospital Fernando Fonseca

Lisbon, Portugal

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples Urine samples

MeSH Terms

Conditions

Hypertension; Sleep Apnea, Obstructive

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Maria E Monteiro, PhD

  Universidade NOVA Lisboa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: November 30, 2020
• Study Start: March 25, 2021
• Primary Completion: September 1, 2023
• Study Completion: March 1, 2024
• Last Updated: December 7, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

PT (5)