- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00420511
Beta-Cell Function and Sitagliptin Trial (BEST) (BEST)
A Randomized Controlled Pilot Study Assessing the Effect of Sitagliptin on the Preservation of Beta-Cell Function in Patients With Type 2 Diabetes
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by progressive deterioration in the function of the pancreatic beta-cells, which are the cells that produce and secrete insulin (the hormone primarily responsible for the handling of glucose in the body). The investigators propose a double-blind, randomized controlled pilot study comparing the effect of sitagliptin (a novel anti-diabetic drug with beta-cell protective potential) versus placebo, on the preservation of beta-cell function over one year in patients with T2DM on metformin, the first-line agent for the treatment of T2DM (ie. the study groups will be (i) sitagliptin and metformin versus (ii) placebo and metformin). This study may demonstrate an important beta-cell protective capacity of sitagliptin.
Hypothesis: In patients with T2DM on metformin, treatment with the DPP-IV inhibitor sitagliptin will preserve pancreatic beta-cell function.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
-
-
Ontario
-
Toronto, Ontario, Canada, M5T 3L9
- Leadership Sinai Centre for Diabetes
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- Men and women between the ages of 30 and 75 inclusive
- Physician-diagnosed type 2 diabetes on 0-2 oral hypoglycemic agents
- Negative for anti-glutamic acid decarboxylase (anti-GAD_ antibodies (to rule out Latent Autoimmune Diabetes of Adults (LADA)
- A1c at screening between 6.5% and 9% inclusive if on no oral hypoglycemic agents or 6.0% and 9.0% inclusive if on 1-2 oral hypoglycemic agents
Exclusion Criteria:
- Current insulin therapy
- Type 1 diabetes or secondary forms of diabetes
- Any major illness with a life expectancy of < 5 years or that may interfere with the patient's participation in the study
- Involvement in any other study requiring drug therapy
- Renal dysfunction as evidenced by serum creatinine >/= 136 umol/L for males or >/= 124 umol/L for females or abnormal creatinine clearance (< 60 ml/min by Modification of Diet in Renal Disease (MDRD) formula)
- Hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, or previous liver transplant) or transaminases > 2.5 times the upper limit of normal
- Excessive alcohol consumption, defined as > 14 alcoholic drinks per week for males and > 9 alcoholic drinks per week for females
- Pregnancy or unwillingness to use reliable contraception. Women should not be planning pregnancy for the duration of the study. Reliable contraception includes: birth control pill, intra-uterine device, abstinence, tubal ligation, partner vasectomy, or condoms with spermicide. Any women who miss a menstrual period or think that they may be pregnant must have a pregnancy test as soon as possible
- History of serious arrhythmia or atrioventricular block on baseline electrocardiogram
- Uncontrolled hypertension (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg)
- Unwillingness to undergo multiple daily insulin injection therapy for 4 weeks
- Unwillingness to perform capillary blood glucose monitoring at least 4 times per day during intensive insulin therapy
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Eksperimentell: Sitagliptin
Sitagliptin 100mg once a day (od) by mouth (po)
|
sitagliptin 100 mg once a day
Andre navn:
metformin 1000 mg twice a day (bid) by mouth (po)
Andre navn:
|
Placebo komparator: Placebo arm
Placebo once a day (od) by mouth (po)
|
metformin 1000 mg twice a day (bid) by mouth (po)
Andre navn:
placebo once a day
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Preservation of Beta-cell Function Measured by Area-under-the-curve (C-peptide/Glucose)/HOMA-IR
Tidsramme: 48 weeks
|
Area-under-the-C-peptide-curve (AUCCpep) and area-under-the-glucose-curve (AUCgluc) from 0 to 240 minutes during meal tests were calculated using the trapezoidal rule.
Insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR).
Beta-cell function was assessed using the ratio of total AUCCpep to AUCgluc divided by HOMA-IR (AUCCpep/gluc/HOMA-IR), a measure of insulin secretion in the context of ambient insulin sensitivity, analogous to the disposition index and adaptation index.
Higher AUCCpep/gluc/HOMA-IR is indicative of better beta-cell function.
|
48 weeks
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Insulinogenic Index Divided by HOMA-IR at 48 Weeks
Tidsramme: 48 weeks
|
Insulinogenic index was calculated as the incremental change in insulin from 0 to 30 minutes divided by the incremental change in glucose over the same period of time.
Insulinogenic index divided by HOMA-IR provides an additional measure of beta-cell function.
A higher value indicates better beta-cell function
|
48 weeks
|
Fasting Blood Glucose at 48 Weeks
Tidsramme: 48 weeks
|
48 weeks
|
|
Area-under-the-glucose-curve (AUCglucose) on Meal Test at 1 Year
Tidsramme: 1 year
|
1 year
|
|
Time to Loss of Glycemic Control
Tidsramme: 1 year
|
1 year
|
|
Proportion of Patients Achieving Sustained Normoglycemia Off Medication at 1-week Post-insulin Therapy
Tidsramme: 1 year
|
1 year
|
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Bernard Zinman, MD, Leadership Sinai Centre for Diabetes, University of Toronto
- Hovedetterforsker: Ravi Retnakaran, MD, Leadership Sinai Centre for Diabetes, University of Toronto
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
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
- Glukosemetabolismeforstyrrelser
- Metabolske sykdommer
- Sykdommer i det endokrine systemet
- Sukkersyke
- Diabetes mellitus, type 2
- Hypoglykemiske midler
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Enzymhemmere
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Proteasehemmere
- Inkretiner
- Dipeptidyl-Peptidase IV-hemmere
- Metformin
- Sitagliptinfosfat
Andre studie-ID-numre
- 065-00
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