GLP-1 Peptide Atlas, by Delfa

CompletedPhase 4

SAFEGUARD: Pleiotropic Effects of Incretin Based Therapies

A Phase IV, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial to Assess the Effect of 12-week Treatment With the Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA) Liraglutide or Dipeptidyl Peptidase-4 Inhibitor (DPP-4i) Sitagliptin on the Cardiovascular, Renal and Gastrointestinal System in Insulin-naïve Patients With Type 2 Diabetes (T2DM).

Lead sponsor

Amsterdam UMC, location VUmc

Assets

Exenatide / GLP-1 / incretin class catch-all / Liraglutide

Listed sites

Recruiting sites

—

Enrollment

actual

Study population

Healthy volunteers, Obesity / overweight, Type 2 diabetes

Key I/E criteria

•BMI 25-40•HbA1c 6.5-9%

Primary endpoints

•Changes from baseline following infusion of GLP-1RA (acute effects)•EGFR, change•Changes from baseline following 12-week treatment

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT01744236

Org study IDDC2012SAFE001

Secondary ID2012-003256-36

Secondary IDU1111-1130-8248WHO Universal Trial Number

Timeline

Milestones

Study first posted2012-12-06estimated

Last update posted2015-12-09estimated

Study start2013-04 (month precision)

Primary completion2015-08actual (month precision)

Study completion2015-08actual (month precision)

Assets

Investigational agents

Exenatide GLP-1 / incretin class catch-all Liraglutide

Study populations

Who this study enrolls

Healthy volunteersObesity / overweightType 2 diabetes

Eligibility

Who can enroll

Minimum age35 Years

Maximum age75 Years

SexAll

Healthy volunteersAccepted

Inclusion criteria

•Age between 35 and 75 years.

•Females must be post-menopausal (no menses >1 year).

•Type 2 diabetes (HbA1c 6.5-9% DCCT or 48-75 mmol/mol IFCC), who are being treated with a stable dose of oral antihyperglycemic agents (either metformin alone, SU alone or a combination of metformin and SU) for at least 3 months prior to inclusion.

•BMI 25 - 40 kg/m2

•Caucasian

•Signed informed consent

Exclusion criteria

•GFR < 60 mL/min/1.73m2

•Current / chronic use of the following medication: thiazolidinediones, GLP-1RA, DPP-4i, glucocorticoids, NSAIDs, insulin, antimicrobial agents, chemotherapeutics or immune suppressants. Subjects on diuretics will only be excluded when these drugs (e.g. hydrochlorothiazide) cannot be stopped for the duration of the study.

•History of or actual pancreatic disease or impaired pancreatic exocrine function

•Active liver disease

•History of or actual malignancy (with the exception of basal cell carcinoma)

•Current urinary tract infection and active nephritis

•Recent (<6 months) history of cardiovascular disease, including acute coronary syndrome, stroke, transient ischemic neurologic disorder or chronic heart failure (New York Heart Association grade II-IV)

•Current atrial fibrillation

•Chronic infectious or auto-immune disease

•Substance and/or alcohol abuse

•History of allergy/hypersensitivity to any of the test agents

•Complaints compatible with or established gastroparesis and/or neurogenic bladder

•Any condition that has been recognized as a contra-indication for the use of GLP-1RA and DPP-4i, as listed in the respective SPCs

•History of or actual (severe) mental illness

•Inability to understand the study protocol and/or inability to give informed consent

•History of claustrophobia or presence of metal objects/implants (because of MRI protocol)

For the preceding Pilot study, we will include:

•Males

•Age between 18 and 50 years

•BMI 25 - 40 kg/m2

•Caucasian

The exclusion criteria for the preceding pilot study are similar to the exclusion criteria of the main study, with the additions of:

•Subjects with a fasting plasma glucose ≥5.6 mmol/L, a 2-hour glucose of ≥7.8 mmol/L after a 75-grams oral glucose tolerance test, or a HbA1c of ≥6.5%

•Subjects using any kind of medication

Endpoints (6)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Renal / kidney

Other (unclassified)

Cardiometabolic biomarkers

Other clinical outcomes

Renal / kidney

2 endpoints

Primary/protocol endpoint

Changes from baseline following infusion of GLP-1RA (acute effects) and the changes from baseline following 12-week treatment with GLP-1RA or DPP-4i (long-term effects) on Glomerular Filtration Rate, measured by the inulin-clearance technique.

Time frame:12 weeks

eGFR, change