Development of a Fast Measurement Technique of Insulin Resistance in Human

NCT01493934 | Completed Phase 1 DMC

• 2 other identifiers: C09-072009-014658-14
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Insulin resistance, characterised by a depressed cellular sensitivity to insulin in insulin-sensitive organs, is a central feature of the metabolic syndrome. In people with no diabetes mellitus, the presence of metabolic syndrome leads to an increase of mortality, whatever the cause, but, as a majority, cardiovascular diseases. In patients with type 2 diabetes mellitus, the presence of a metabolic syndrome leads to an increase in major adverse cardiovascular events. The prevalence of metabolic syndrome is led to grow in a near future, because of the increase of diabetes mellitus and obesity prevalence. Actually, there is no simple tool to measure insulin resistance. The gold standard technique remains the hyperinsulinemic euglycemic clamp. However, the complexity and length of this technique render it unsuitable for routine clinical use. Many methods or index have been proposed to assess insulin resistance in human, but none have shown enough relevance to be used in clinical use. Within the investigators U877 INSERM team, the investigators previously performed in vivo biodistribution studies with 6-DIG (6-deoxy-6-iodo-D-glucose), a new tracer of glucose transport, radiolabelled with123 iodine, with and without insulin, on the one hand in genetically diabetic mice (db/db), consequently having a severe insulin resistance and in the other hand in rats with acquired insulin resistance after a "fructose diet". The investigators have demonstrated that 6-DIG is able to identify in vivo slight glucose transport variations in insulin sensible organs. Then, the investigators developed a fast and simple imaging protocol with a small animal gamma camera, which allows the obtaining of an insulin resistance index for each organ, directly transferable to human. The investigators project is to transfer to human this measurement technique, perfectly validated in animal. The main goal of this monocentric phase I-II study is to evaluate the tolerance to the insulin resistance measurement technique with 6DIG scintigraphy, in healthy volunteers and in diabetic patients. The investigators plan to enrol 6 healthy volunteers and 6 type 2 diabetic patients. The investigators secondary goals will be to evaluate feasibility and reproducibility of the measurement technique, to follow pharmacokinetic and to assess efficacy of 6-DIG to measure insulin resistance.

Conditions

Type 2 Diabetes Mellitus

Keywords

metabolic syndrome; type 2 diabetes mellitus; insulin resistance; Scintigraphy

Outcome Measures

Primary Outcomes (1)

• Change of glycemia

  Assessment of tolerance to insulin resistance measurement technique with 6-DIG scintigraphy, in healthy volunteers * clinical tolerance to 6-DIG infusion * clinical and biological tolerance to insulin infusion * evaluation of dosimetry

  Before inclusion in clinical trial, Before radiotracer injection, After radiotracer injection (time: 30s, 1', 2',5',10',15',25', 1 hour, 2 hours, 4 hours, 8 hours, 24 hours)

Secondary Outcomes (4)

• insulinemia

  Before inclusion in clinical trial, Before radiotracer injection, After radiotracer injection (time: 30s, 1', 2',5',10',15',25', 1 hour, 2 hours, 4 hours, 8 hours, 24 hours)

• clinical side effects

  Before inclusion in clinical trial, Before radiotracer injection, After radiotracer injection (time: 30s, 1', 2',5',10',15',25', 1 hour, 2 hours, 4 hours, 8 hours, 24 hours)

• dosimetry

  during the 24 hours following injection of 6-DIG

• insulin resistance

  0-15 minutes following 6-DIG infusion

Study Arms (2)

Healthy volunteers

ACTIVE COMPARATOR

First injection in human, on 6 healthy volunteers, sequentially : volunteer number1, then volunteers n°2 to n° 6, before infusion in type 2 diabetic patients.

Drug: injection of 6-DIG

type 2 diabetic patients

EXPERIMENTAL

After completion of the study for the 6 healthy volunteers, infusion in 6 type 2 diabetic patients.

Drug: injection of 6-DIG

Interventions

injection of 6-DIG DRUG

Unique injection dose of 92.5 MBq

Healthy volunteers; type 2 diabetic patients

Eligibility Criteria

• Age: 35 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers
• Aged between 35 et 60 years old
• Body mass index between 20 and 25
• Waist measurement \< 94 cm for men and \< 80 cm for women
• Normal basal glycemia, between 3,8 and 5,8 mmol/l
• Normal basal insulinemia, between 3 and 13 μUI/ml
• HbA1c \< 6%
• Total cholesterol \< 2 g/l
• LDL cholesterol \< 1,6 g/l
• HDL cholesterol 0,4 g/l for men and 0,5 g/l for women
• Triglyceride level \< 1,5 g/l
• For women not menopausal since at last one year or not surgically sterilised:
• On-going contraception, physical or hormonal, excepted local methods (spermicidal, diaphragm, condom, cape)
• Type 2 diabetic patients
• Aged between 35 et 60 years old

You may not qualify if:

• Diabetes mellitus previously known
• Other on-going progressive illness
• Psychiatric illness, needing a chronic treatment
• Previous history of myocardial infarction, coronary artery disease, cardiac rhythm troubles, stroke, epilepsy, cranial trauma, pituitary surgery, disease likely to reduce the ability of absorption, diffusion or excretion of the radiotracer.
• Severe hypertension defined by par SAP \> 180 mmHg and/or DAP \> 110 mmHg
• Allergy to one of the components of the products used during the study
• Treatment likely to interfere with glucose metabolism
• Alcohol or drug intoxication
• Vegetarian or restrictive low-calory diet,
• Pregnant, parturient or breast-feeding women,
• Inappropriate way of life
• Type 2 diabetic patients.
• Previous history of myocardial infarction
• Severe hypertension defined by par SAP \> 180 mmHg and/or DAP \> 110 mmHg
• Previous history of coronary artery disease, cardiac rhythm troubles, stroke, epilepsy, cranial trauma, pituitary surgery, disease likely to reduce the ability of absorption, diffusion or excretion of the radiotracer.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Service de Biophysique et Médecine Nucléaire, CHU de Grenoble

Grenoble, France

Location

Related Publications (1)

• Calizzano A, Perret P, Desruet MD, Ahmadi M, Reboulet G, Djaileb L, Vanzetto G, Fagret D, Barone-Rochette G, Ghezzi C. Safety, Biodistribution, and Dosimetry of 123I-6-Deoxy-6-Iodo-D-Glucose, a Tracer of Glucose Transport, in Healthy and Diabetic Volunteers. Clin Nucl Med. 2019 May;44(5):386-393. doi: 10.1097/RLU.0000000000002510.

  PMID: 30888989 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Metabolic Syndrome; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Study Officials

• Alex Calizzano, MD

  Institut National de la Santé Et de la Recherche Médicale, France

  STUDY DIRECTOR

• Alex Calizzano, MD

  Institut National de la Santé Et de la Recherche Médicale, France

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2010
• First Posted: December 16, 2011
• Study Start: April 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: August 27, 2025

Record last verified: 2016-02

Locations

FR (1)