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Completed

NCT Number: NCT03912012

Pilot Study DiaDEP

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.

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Key information

Age range

10 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hopital Femme Mère Enfant - Groupement Hospitalier Est

Bron, 69677, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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;

Treatment and study plan

Iohexol renal clearance measurement

Drug

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

microcirculation assessment through Laser Doppler associated to iontophoresis.

Device

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

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

Device

carotid ultrasound (during Day 1)

Blood sampling

Biological

37 mL of blood sample will be performed at Day 1

Urine sampling

Biological

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

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

Device

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

Dual-energy X-ray (DXA)

Radiation

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

Primary outcomes

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

    Time frame: Day 1

    assessed through Iohexol renal clearance measurement

Secondary outcomes

  1. Endothelial function in the forearm.

    Time frame: Day 1

    Endothelial function will be evaluated by the microcirculation assessment through Laser Doppler associated to iontophoresis of acetylcholine.

  2. Intima media thickness

    Time frame: Day 1

    The intima media thickness will be performed by Echo Doppler of both right and left common carotid

  3. arterial blood pressure

    Time frame: Day 1

    arterial blood pressure measurement

  4. Bone mass

    Time frame: Day 1

    Bone mass will be performed by Dual-energy X-ray absorptiometry (DXA) on both spine and whole body.

  5. bone density

    Time frame: Day 1

    bone density will be performed by Dual-energy X-ray absorptiometry (DXA) on both spine and whole body.

  6. quantization of bone mineral content

    Time frame: Day 1

    quantization of bone mineral content will be performed by Dual-energy X-ray absorptiometry (DXA) on both spine and whole body.

  7. Volumetric compartmental density

    Time frame: Day 1

    Volumetric compartmental density will be performed by High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) on radius and tibia (Right tibia and non-dominant arm radius). (Unless there is a history of fracture for one of those bones, in which case the opposite side will be studied instead.)

  8. trabecular microarchitecture

    Time frame: Day 1

    trabecular microarchitecture will be performed by High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) on radius and tibia (Right tibia and non-dominant arm radius). (Unless there is a history of fracture for one of those bones, in which case the opposite side will be studied instead.)

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study title

Endothelial Dysfunction Could be an Early Biomarker of Renal Impairment in Children and Adolescent With Type 1 Diabetes. Pilot Study DiaDEP

Acronym: DiaDEP

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Apr 11, 2019
Registry last updated
Feb 28, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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