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Development of a Fast Measurement Technique of Insulin Resistance in Human (GLUCIMAG)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by Institut National de la Santé Et de la Recherche Médicale, France.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier:
NCT01493934
First received: April 28, 2010
Last updated: October 8, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: injection of 6-DIG
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Development of a Fast Measurement Technique of Insulin Resistance in Human, With 123-6-deoxy-6 Iodo-D-glucose, a New Tracer of Glucose Transport

Resource links provided by NLM:


Further study details as provided by Institut National de la Santé Et de la Recherche Médicale, France:

Primary Outcome Measures:
  • Change of glycemia [ Time Frame: 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) ] [ Designated as safety issue: Yes ]

    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


Secondary Outcome Measures:
  • insulinemia [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
  • clinical side effects [ Time Frame: 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) ] [ Designated as safety issue: Yes ]
    hypoglycemia symptoms

  • dosimetry [ Time Frame: during the 24 hours following injection of 6-DIG ] [ Designated as safety issue: Yes ]
    organs biodistribution of radioactivity

  • insulin resistance [ Time Frame: 0-15 minutes following 6-DIG infusion ] [ Designated as safety issue: No ]
    scintigraphic measurement of glucose transport in heart before and after infusion of insulin


Estimated Enrollment: 12
Study Start Date: April 2010
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Healthy volunteers
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
Unique injection dose of 92.5 MBq
Experimental: type 2 diabetic patients
After completion of the study for the 6 healthy volunteers, infusion in 6 type 2 diabetic patients.
Drug: injection of 6-DIG
Unique injection dose of 92.5 MBq

  Eligibility

Ages Eligible for Study:   35 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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
  • Stable type 2 diabetes mellitus: no ketoacidosis sign during last month
  • HbA1c between 6 and 8% during the 3 months before study inclusion
  • Monotherapy by metformin or diet only
  • 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)

Exclusion Criteria:

  • 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
  • Nuclear medicine examination during the 30 days prior to study inclusion
  • 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.
  • Psychiatric illness, needing a chronic treatment
  • On-going insulin treatment
  • On-going treatment other than metformin, likely to interfere with glucose metabolism
  • Previous history of disease likely to reduce the ability of absorption, diffusion or excretion of the radiotracer
  • Allergy to one of the components of the products used during the study
  • Nuclear medicine examination during the 30 days prior to study inclusion
  • Alcohol or drug intoxication
  • Vegetarian or restrictive low-calory diet,
  • Pregnant, parturient or breast-feeding women,
  • Inappropriate way of life
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01493934

Contacts
Contact: Alex Calizzano, MD +334 76 76 54 55 Acalizzano@chu-grenoble.fr

Locations
France
Service de Biophysique et Médecine Nucléaire, CHU de Grenoble Recruiting
Grenoble, France
Contact: Alex Calizzano, MD    +334 76 76 54 55    acalizzano@chu-grenoble.fr   
Principal Investigator: Alex Calizzano, MD         
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
Study Director: Alex Calizzano, MD Institut National de la Santé Et de la Recherche Médicale, France
Study Chair: Alex Calizzano, MD Institut National de la Santé Et de la Recherche Médicale, France
  More Information

No publications provided

Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT01493934     History of Changes
Other Study ID Numbers: C09-07, 2009-014658-14
Study First Received: April 28, 2010
Last Updated: October 8, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:
metabolic syndrome
type 2 diabetes mellitus
insulin resistance
Scintigraphy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Insulin Resistance
Endocrine System Diseases
Glucose Metabolism Disorders
Hyperinsulinism
Metabolic Diseases
Insulin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014