- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01526720
The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS)
The Verona Newly Diagnosed Type 2 Diabetes Study. Construction of a Biobank of Diabetes Related Genotypes and Phenotypes
Studieoversikt
Status
Forhold
Detaljert beskrivelse
The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) is an ongoing study aiming at building a biobank of patients with newly diagnosed type 2 diabetes mellitus. All patients referred to the Division of Endocrinology and Metabolic Diseases of University of Verona School of Medicine, whose diabetes has been diagnosed in the last six months, are asked to participate in this research. The clinical evidence on which the diagnosis of type 2 diabetes has been made is reviewed and the diagnosis confirmed, according to the current criteria of American Diabetes Association. Patients already treated with antidiabetic drugs undergo a treatment washout of at least one week before metabolic tests are performed. Among the exclusion criteria are age > 75 years, non-Italian ancestry, insulin treatment, presence of anti-GAD antibodies, malignancies, and any condition severely impairing liver and/or kidney function.
All subjects consume a weight-maintaining diet containing 200-250 g of carbohydrate/day for at least three days before studies. Body weight must be stable in all subjects for at least 1 month before studies. No subject should participate in any heavy exercise. Each subject gives informed written consent before participating in the research, which was approved by the Human Investigation Committee of the Verona City Hospital. Measurements of standard clinical phenotypes are collected in all patients. Other diabetes related phenotypes may be collected if their determination is available.
Metabolic tests are carried out on two separate days in random order. On both days, patients are admitted to the Metabolic Clinic Research Center at 07:30 after an overnight fast. All studies are carried out in a quiet, temperature controlled (22° C) room. On one day an oral glucose tolerance test (OGTT) (75 g) is performed to assess beta cell function. On a separate day, a euglycemic insulin clamp is performed to assess insulin sensitivity.
When age of onset and distribution of the disease in the pedigree suggest a potentially monogenic disorder, the relatives of the proband are asked to participate in the study by allowing the collection of standard clinical information and of a fasting blood sample for genetic and phenotypic determinations.
-OGTT: For ethical reasons, the OGTT cannot performed in patients presenting with fasting plasma glucose higher than 15 mmol/l. During the entire test patients are sitting in a comfortable cardiac chair. One teflon (21 g) venous catheter is inserted into an antecubital vein for blood sampling and kept patent with heparinized normal saline solution. After a 30' rest to establish baseline and after collecting a 20 cc blood sample for leukocyte DNA extraction, at time = 0' subjects ingest 75 g of glucose in 300 ml of water over 5 min. Blood samples to measure glucose, C-peptide and insulin concentrations are collected at times -10', 0', +15', +30', +45', +60', +90', +120', +150', +180', +210' and +240', +270' and +300'. Urines are collected to measure glycosuria.
-Euglycemic Insulin Clamp: During the entire test patients are lying in bed. One teflon catheter is introduced into an antecubital vein for the infusion of test substances. Another teflon catheter is placed retrogradely into a wrist vein for sampling arterialized venous blood, according to the "hot box" technique. After a 30' rest in bed to establish baseline, indirect calorimetry (at least 40') is performed. At the end of calorimetric measures, baseline blood samples are collected and a standard euglycemic insulin clamp is carried out. After an insulin intravenous prime of 4.8 pmol/min/m^2 BSA and a subsequent continuous infusion of 240 pmol/min/m^2 BSA, plasma glucose is allowed to decline until it reaches 5.5 mmol/l, after which glucose clamping starts with a glucose concentration goal of 5 mmol/l. The duration of the glucose clamp is at least of 120', but it is prolonged, if and as needed, to ensure at least 60' of insulin clamp at euglycemia in each patient. Timed blood samples were collected to measure hormone and substrate levels. In the last 45' of the clamp indirect calorimetry is repeated to assess substrate oxidation and energy production rates. Urine is collected to measure urea excretion rate.
In both metabolic tests, all blood samples are collected in pre-chilled tubes and readily spun at 1,500 g. Plasma and serum specimens are stored at -80° C.
-Analytical procedures: Plasma glucose concentration is measured in duplicate at bedside. Serum C-peptide and insulin concentrations are measured by chemiluminescence. Glycated hemoglobin and serum lipids were measured by standard in-house methods. GAD-antibodies are measured by immunoradiometry (CentAK, Medipan, Germany), according to manufacturer's instructions.
-Genotyping: A leukocyte DNA sample is collected in each subject and the DNA is extracted through standard salting out method. Genotyping is performed by RFLP (Restriction Fragment Length Polymorphism), which consists in a PCR (Polymerase Chain Reaction) followed by proper enzymatic digestion and resolution on agarose gel. Alternatively, it is performed were assessed by the high-throughput genotyping Veracode technique (Illumina Inc, CA), applying the GoldenGate Genotyping Assay according to manufacturer's instructions.
Studietype
Registrering (Forventet)
Kontakter og plasseringer
Studiekontakt
- Navn: Riccardo C Bonadonna, MD
- Telefonnummer: +39 045 8123110
- E-post: riccardo.bonadonna@univr.it
Studiesteder
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-
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Verona, Italia, 37126
- Rekruttering
- Division of Endocrinology and Metabolic Diseases - University Hospital of Verona
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Prøvetakingsmetode
Studiepopulasjon
Group A: all patients referred to the Division of Endocrinology and Metabolic Diseases of University of Verona School of Medicine, whose diabetes has been diagnosed in the last six months, are asked to participate in this research.
Group B: Relatives of patients with potentially monogenic newly diagnosed type 2 diabetes
Beskrivelse
Inclusion Criteria:
- Type 2 diabetes mellitus, whose diagnosis has been made in the last six months before the first access to the Division of Endocrinology and Metabolic Diseases of University of Verona School of Medicine;
- Relatives of patients with potentially monogenic newly diagnosed type 2 diabetes
Exclusion Criteria:
- Age > 75 years
- Non-Italian ancestry
- Insulin treatment
- Presence of anti-GAD antibodies
- Malignancies
- Any condition severely impairing liver and/or kidney function
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Observasjonsmodeller: Familiebasert
- Tidsperspektiver: Tverrsnitt
Kohorter og intervensjoner
Gruppe / Kohort |
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Group A: Diabetic
Newly diagnosed type 2 diabetic patients (i.e.
diagnosis made no more than 6 months before recruitment)
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Group B: Relatives
Relatives of patients with potentially monogenic newly diagnosed type 2 diabetes
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Genetic basis of beta cell function
Tidsramme: Baseline and during the 75 g oral glucose challenge. Subjects will be followed for the duration of their stay in the Metabolic Clinical Research Center (average expected stay: 6 hours)
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Investigators genotype diabetes risk loci and relate them to two main beta cell metrics, after correction for insulin sensitivity:
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Baseline and during the 75 g oral glucose challenge. Subjects will be followed for the duration of their stay in the Metabolic Clinical Research Center (average expected stay: 6 hours)
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Genetic basis of insulin sensitivity
Tidsramme: Baseline and during the euglycemic insulin clamp. Subjects will be followed for the duration of their stay in the Metabolic Clinical Research Center (average stay: 4 hours)
|
Investigators genotype diabetes risk loci and relate them, after correcting for the influence of other genetic and nongenetic modifiers, to one metric of clamp derived insulin sensitivity: 1. M value, which quantifies whole body net glucose disposal during euglycemic hyperinsulinemia |
Baseline and during the euglycemic insulin clamp. Subjects will be followed for the duration of their stay in the Metabolic Clinical Research Center (average stay: 4 hours)
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Studiestol: Enzo Bonora, MD PhD, Section of Endocrinology, Diabetes and Metabolism - Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata, Verona, Italy
- Hovedetterforsker: Riccardo C Bonadonna, MD, Section of Endocrinology, Diabetes and Metabolism - Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata, Verona, Italy
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Bonora E, Trombetta M, Dauriz M, Travia D, Cacciatori V, Brangani C, Negri C, Perrone F, Pichiri I, Stoico V, Zoppini G, Rinaldi E, Da Prato G, Boselli ML, Santi L, Moschetta F, Zardini M, Bonadonna RC. Chronic complications in patients with newly diagnosed type 2 diabetes: prevalence and related metabolic and clinical features: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 9. BMJ Open Diabetes Res Care. 2020 Aug;8(1):e001549. doi: 10.1136/bmjdrc-2020-001549.
- Trombetta M, Dauriz M, Bonetti S, Travia D, Boselli L, Santi L, Bonora E, Bonadonna RC. Is common genetic variation at IRS1, ENPP1 and TRIB3 loci associated with cardiometabolic phenotypes in type 2 diabetes? An exploratory analysis of the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 5. Nutr Metab Cardiovasc Dis. 2016 Mar;26(3):232-8. doi: 10.1016/j.numecd.2016.01.002. Epub 2016 Jan 14.
- Dauriz M, Trombetta M, Boselli L, Santi L, Brangani C, Pichiri I, Bonora E, Bonadonna RC. Interleukin-6 as a potential positive modulator of human beta-cell function: an exploratory analysis-the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 6. Acta Diabetol. 2016 Jun;53(3):393-402. doi: 10.1007/s00592-015-0807-z. Epub 2015 Nov 4.
- Zoppini G, Cacciatori V, Raimondo D, Gemma M, Trombetta M, Dauriz M, Brangani C, Pichiri I, Negri C, Stoico V, Bergamini C, Targher G, Santi L, Thomaseth K, Bellavere F, Bonadonna RC, Bonora E. Prevalence of Cardiovascular Autonomic Neuropathy in a Cohort of Patients With Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS). Diabetes Care. 2015 Aug;38(8):1487-93. doi: 10.2337/dc15-0081. Epub 2015 Jun 11.
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Forventet)
Studiet fullført (Forventet)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- CE-955
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