Pilot Study DiaDEP

NCT03912012 | Completed

• 1 other identifier: 69HCL17_0518
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

With an increased incidence of pediatric type 1 diabetes (T1D) and a decrease in age at diagnosis, children are exposed to complications such as renal impairment at a very young age. The current biomarker used to diagnose renal impairment is microalbuminuria, but it's a late marker. Early screening is a major issue to reduce T1D consequences. Early glomerular hyperfiltration (GHF) could participate in the development and progression of nephropathy. Hyperfiltration has also been associated with a systemic endothelial dysfunction and with changes in arterial stiffness, suggesting, at least to a certain extent, a state of generalized vascular dysfunction. Diabetes is responsible for very early neurovascular dysfunctions, detectable with techniques to evaluate cutaneous neurovascular interaction. Those should help bringing to light very early microcirculation impairment, particularly precocious endothelial dysfunction (ED). No study about correlation between GHF and ED is currently available. The hypothesis assessed is those of a strong correlation between ED and GHF in children and adolescent with a story of T1D for at least 10 years. This pilot study should allow assessing ED's and GHF's proportions in our population, in order to conduct a larger study to prove, in a prospective way, the prognostic value of ED in the apparition of nephropathy, taking into count other factors such as diabetes duration or stability. This measure could be included in the global evaluation of microangiopathy risk in children and then take action to prevent negative outcomes. The second aspect of this study is the assessment of other functions and metabolisms possibly impaired in T1D: osseous microarchitecture, vitamin D status and precocious evaluation of macro angiopathy through intima media thickness measurement. Long term diabetes in children is associated with shorter and leaner bones, despite a correct mineralization, a reduced bone density and a fracture risk increased six fold. Bone status in the population will be evaluated through the study of bones microarchitecture via HR-pQCT (High Resolution peripheral Quantitative Computed Tomography) on both tibia and radius, dual-energy X-ray absorptiometry (DXA), and bone turn over biochemical markers. Results on bone microarchitecture in a preexisting cohort of healthy children and adolescents will be used to compare results.

Conditions

Diabetes Mellitus, Type 1; Type1diabetes

Keywords

Diabetes mellitus type 1; Type 1 diabetes; diabetes; pediatrics; Glomerular hyperfiltration; endothelial dysfunction; children; adolescent

Outcome Measures

Primary Outcomes (1)

• Glomerular hyper filtration (Glomerular filtration > 135 mL/min/1,73 m2)

  assessed through Iohexol renal clearance measurement

  Day 1

Secondary Outcomes (8)

• Endothelial function in the forearm.

  Day 1

• Intima media thickness

  Day 1

• arterial blood pressure

  Day 1

• Bone mass

  Day 1

• bone density

  Day 1

Study Arms (1)

Children and adolescent with a history of type 1 diabetes

OTHER

Children and adolescent from 10 to 18 years old, with a history of type 1 diabetes for at least 10 years. Glomerular hyper filtration and endothelial dysfunction will be evaluate.

Drug: Iohexol renal clearance measurement; Device: microcirculation assessment through Laser Doppler associated to iontophoresis.; Device: Cardiovascular assessment though Intima-media Thickness and Extra-media Thickness measurement; Biological: Blood sampling; Biological: Urine sampling; Device: High-resolution peripheral quantitative computed tomography (HR-pQCT); Radiation: Dual-energy X-ray (DXA)

Interventions

Iohexol renal clearance measurement DRUG

intravenous injection of Iohexol (Omnipaque 300mg) with blood sampling at 0, 120, 180 and 240 minutes (during Day 1.

Children and adolescent with a history of type 1 diabetes

microcirculation assessment through Laser Doppler associated to iontophoresis. DEVICE

endothelial function evaluated following a protocol of iontophoresis of acetylcholine (during Day 1).

Children and adolescent with a history of type 1 diabetes

Cardiovascular assessment though Intima-media Thickness and Extra-media Thickness measurement DEVICE

carotid ultrasound (during Day 1)

Children and adolescent with a history of type 1 diabetes

Blood sampling BIOLOGICAL

37 mL of blood sample will be performed at Day 1

Children and adolescent with a history of type 1 diabetes

Urine sampling BIOLOGICAL

The urinary collection will be done during the Day 1, on the first morning urination

Children and adolescent with a history of type 1 diabetes

High-resolution peripheral quantitative computed tomography (HR-pQCT) DEVICE

assessment of the Body Mass Index by HR-pQCT (during the Day 1)

Children and adolescent with a history of type 1 diabetes

Dual-energy X-ray (DXA) RADIATION

assessment of bone parameters by DXA (during the Day 1)

Children and adolescent with a history of type 1 diabetes

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Aged ≥ 10 et \< 18 years old
• Type 1 diabetes diagnosed more than 10 years previously.
• Written informed consent signed by both parents or legal representatives, child or adolescent's agreement.
• Health cover

You may not qualify if:

• Associated pathology with a potential impact on cutaneous microcirculation or renal function.
• Aspirin or other non-steroid anti-inflammatory treatment with potential impact on endothelial function in the 3 weeks preceding the visit.
• Examination with injection of contrast agent during the last 48 hours
• Smoking
• Ongoing pregnancy or breast feeding
• Hypersensitivity to acetylcholine
• Contraindication to Iohexol
• Ongoing treatment with growth hormone, non-inhaled corticosteroids or anti-calcineurins;
• History of treatment with oral corticosteroids (not inhaled) more than 3 successive months regardless of seniority;
• Paracetamol treatment less than a week old;

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hopital Femme Mère Enfant - Groupement Hospitalier Est

Bron, 69677, France

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

Blood Specimen Collection; Absorptiometry, Photon

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Radiography; Diagnostic Imaging; Densitometry; Photometry; Chemistry Techniques, Analytical

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: April 11, 2019
• Study Start: July 9, 2019
• Primary Completion: November 20, 2020
• Study Completion: November 20, 2020
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

FR (1)