Effect of Acute Hypoxia on Renal Hemodynamic in Healthy Volunteers, Patients With Diabetes and Patients With Diabetes and Kidney Disease

Official title

Effect of Acute Hypoxia on Renal Hemodynamic in Healthy Volunteers, Patients With Diabetes and Patients With Diabetes and Kidney Disease : Pilot Study.

Overview

Diabetes mellitus is a non-transmissible disease whose incidence is growing worldwide . This pathology is defined by a chronic hyperglycaemia linked to a deficiency of either insulin secretion or its action or both. This increased prevalence is linked to the growing of the obese population on one hand, and to the ageing of the population, on the other hand, which is associated with an increased prevalence of metabolic diseases. The number of patients with diabetes, particularly type 2 diabetes (T2D) is regularly increasing. In France, the prevalence of diabetes is 4- 6% of the adult population. Diabetic kidney disease (DKD) is a growing public health problem and therefore constitutes a major factor in progressive kidney disease. DKD has become the leading cause of end stage kidney disease (ESKD), requiring dialysis or transplantation. Current routine screening for DKD is limited to detecting of impaired glomerular filtration rate (GFR) and/or elevated albuminuria, typically manifests in later stages of DKD. Therefore, the current methods to screen for DKD lack the resolution to capture the earliest functional changes associated with DKD. Chronic renal hypoxia plays a crucial role in the development and progression of DKD and may affect Renal hemodynamic. The aim to assess the feasibility of the measure of hypoxa-induced renal hemodynamics parameters.

Interventions

• Other Hypoxia administration study group
  Acute 2-hour hypoxia (14.5%FiO2 corresponding to 3000m altitude)
• Combination product Renal clairance study
  Assessment of renal clearance by measuring Glomerular Filtration Rate (GFR) after two agents infusion: * Aminohippurate Sodium (or or para-aminohippuric acid \[PAH\]) Inj 20% Diagnostic agent used to measure effective renal plasma flow (ERPF) * Iohexol Inj 300 MG/ML Diagnostic agent used to measure glomerular filtration rate (GFR)

Primary outcome measures

• Effective Renal Plasma Flow (ERPF) [Time frame: 5 hours]
• Glomerular Filtration Rate [Time frame: 5 hours]

Secondary outcome measures (5)

• circulating and urinary mitochondrial metabolites [Time frame: 8 days]
• blood pressure [Time frame: 5 hours]
• heart rate [Time frame: 5 hours]
• Lake Louise Questionnaire [Time frame: 5 hours]
• Oxygen saturation [Time frame: 5 hours]

Eligibility criteria

Inclusion criteria

For all participant :

• No history of respiratory diseases
• Affiliated person or beneficiary of the French social security scheme.
• signed informed consent

Group 1 ( For healthy volunteers):

• \[18; 40\] years old
• No history of diabetes
• No acute/long term > 3 months drug use except contraception
• BMI: \[18,5 - 29,9\]kg/m2
• eGFR > 60ml/min/1.73m2
• Normal to midly increased albuminuria: defined as ACR < 3 mg/mmol

For all the patients with T2D (group 2 and 3):

• Diagnosed T2D according to ADA criteria
• \[35; 75\] years old
• Stable treatment of diabetes and/or antihypertension for at least 2 months prior to inclusion
• No proliferative diabetic retinopathy

Group 2 - For patients with T2D and no DKD:

• eGFR > 60ml/min/1.73m2 and
• Normal to midly increased albuminuria: defined as ACR < 3 mg/mmol

Group 3 - For patients with DKD:

• eGFR \[45-60 ml/min/1.73m2\] and/or
• Moderately to severely increased ACR ≥ 3 mg/mmol

Exclusion criteria

For all participants:

• Active smoking
• Contraindication to any of the agent (PAH, or iohexol or gadolinium) used in the study.
• Contraindication to cardiac MRI, renal MRI, respiratory tests,
• History acute coronary syndrome or coronary revascularization
• Recent (<6 months) history of: Heart failure requiring hospitalisation or Stroke or transient ischemic neurologic disorder
• Severe unstable hypertension (≥180 mmHg systolic or ≥110 mmHg diastolic blood pressure)
• Resting oxygen saturation <95% at baseline
• Any concomitant disease or condition that may interfere with the safety or the possibility for the patient to comply with or complete the study protocol.
• History of severe mountain sickness (dizziness, headache, nausea/vomiting and incapaciting fatigue)
• Consumption of SGLT2 inhibitors
• Concurrent participation in another clinical research study
• Pregnant or breastfeeding women, women of childbearing age who do not have effective contraception
• Persons benefiting from enhanced protection under french national law
• Persons under psychiatric care who are unable to give their consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

France · 1 center

• Centre Investigation Clinique CIC1402 - CHU Poitiers — Poitiers

Identifiers

NCT: NCT06846034 · DIAKIPOX

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗