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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetes; Hypoxia; Diabetic Kidney Disease; Diabetic Nephropathies; Healthy Volunteer
• Intervention / Treatment: Other: Hypoxia administration study group; Combination product: Renal clairance study

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emilie RABOIS, MSc; Phone Number: +330549444686; Email: emilie.rabois@chu-poitiers.fr
• Study Contact Backup: Name: Céline DELETAGE METREAU, PhD; Email: Celine.DELETAGE-METREAU@chu-poitiers.fr

Study Locations

• France
  • Poitiers, France
    • Recruiting
    • Centre Investigation Clinique CIC1402 - CHU Poitiers
    • Contact: Emilie RABOIS, MSc; Phone Number: +33(0)549444689; Email: emilie.rabois@chu-poitiers.fr
    • Contact: Pierre Jean SAULNIER, MD PhD
    • Contact: Christophe RAULT, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For all participant :

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

Group 1 ( For healthy volunteers):

1. [18; 40] years old
2. No history of diabetes
3. No acute/long term > 3 months drug use except contraception
4. BMI: [18,5 - 29,9]kg/m2
5. eGFR > 60ml/min/1.73m2
6. Normal to midly increased albuminuria: defined as ACR < 3 mg/mmol

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

1. Diagnosed T2D according to ADA criteria
2. [35; 75] years old
3. Stable treatment of diabetes and/or antihypertension for at least 2 months prior to inclusion
4. 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:

1. Active smoking
2. Contraindication to any of the agent (PAH, or iohexol or gadolinium) used in the study.
3. Contraindication to cardiac MRI, renal MRI, respiratory tests,
4. History acute coronary syndrome or coronary revascularization
5. Recent (<6 months) history of: Heart failure requiring hospitalisation or Stroke or transient ischemic neurologic disorder
6. Severe unstable hypertension (≥180 mmHg systolic or ≥110 mmHg diastolic blood pressure)
7. Resting oxygen saturation <95% at baseline
8. 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.
9. History of severe mountain sickness (dizziness, headache, nausea/vomiting and incapaciting fatigue)
10. Consumption of SGLT2 inhibitors
11. Concurrent participation in another clinical research study
12. Pregnant or breastfeeding women, women of childbearing age who do not have effective contraception
13. Persons benefiting from enhanced protection under french national law
14. Persons under psychiatric care who are unable to give their consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: acute hypoxia; The participant will be exposed to 2 sequences : a 3-hour normoxia period and then a 2-hour hypoxia (FiO2=14.26% corresponding to 3000m altitude) period.

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effective Renal Plasma Flow (ERPF)	Measured by PAH clearance	5 hours
Glomerular Filtration Rate	Measured by Iohexol Clearance	5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
circulating and urinary mitochondrial metabolites	To investigate change of blood or urine metabolites : 2-ethyl 3-OH propionate, 3-hydroxy propionate, 3-hydroxy isovalerate, 3-methyl-crotonyl glycine, 3-hydroxy isobutyrate, Tiglyglycine, Aconitic acid, Citric acid, Glycolic acid, Homovanillic acid, Uracil, 3-methyl adipic acid.	8 days
blood pressure	mean arterial pressure	5 hours
heart rate	heart rate	5 hours
Lake Louise Questionnaire	The Lake Louise Scoring was developed to assess the symptoms of acute mountain sickness in adults. It consist of 4 questions, each rated on a likert-type scale with 0-3 response options. Lower scores men a better outcome.	5 hours
Oxygen saturation	SpO2	5 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal Oxygenation Availability	Blood oxygen level dependent (BOLD) MRI	60 minutes
Cardiac Oxygenation Availability	Blood oxygen level dependent (BOLD) MRI	60 minutes

Collaborators and Investigators

• Sponsor: Poitiers University Hospital
• Investigators: Principal Investigator: Pierre Jean SAULNIER, MD PhD, CHU Poitiers

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: February 13, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): February 25, 2025

Study Record Updates

• Last Update Posted (Actual): April 9, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Complications; Signs and Symptoms, Respiratory; Diabetes Mellitus; Hypoxia; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: DIAKIPOX

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No