Kynurenine/Tryptophan Ratio in Hypertension Associated to Obstructive Sleep Apnea

Hypertension Secondary Clinical Trial

— KYNTOSA  

Official title:

Relevance of the Ratio Kynurenine/Tryptophan to Characterize Hypertension Associated to Obstructive Sleep Apnea (KYNTOSA)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04646902
• Other study ID #: Kyntosa_02_20200428
• Secondary ID: PTDC/MED-TOX3041
• Status: Active, not recruiting
• Start date: March 25, 2021
• Est. completion date: March 1, 2024

Study information

• Verified date: December 2023
• Source: Universidade Nova de Lisboa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 203
• Est. completion date: March 1, 2024
• Est. primary completion date: September 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hypertension
• Hypertension Secondary
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Locations

Country	Name	City	State
Portugal	Centro Hospitalar de Lisboa Central	Lisboa
Portugal	Centro Hospitalar Lisboa Ocidental	Lisboa
Portugal	Hospital Beatriz Ângelo	Lisboa
Portugal	Hospital da Luz	Lisboa
Portugal	Hospital Fernando Fonseca	Lisboa

Sponsors (6)

Lead Sponsor	Collaborator
Universidade Nova de Lisboa	Centro Hospitalar de Lisboa Central, Centro Hospitalar Lisboa Ocidental, Hospital Beatriz Ângelo, Hospital da Luz, Portugal, Hospital Fernando Fonseca

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kynurenine / Tryptophan ratio	Ratio between kynurenine and tryptophan concentrations	Day 1 (visit 1)
Secondary	Concentrations of metabolites	The relevant metabolites and their concentration will be identified by Partial Least Square Discriminant Analysis (PLS-DA) applied to non-targeted metabolomics.	Day 1 (visit 1)