Clinical trial NCT02150707: The Differential Effects of Diabetes Therapy on Inflammation
Official title: The Differential Effects of Diabetes Therapy on Inflammation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetic Nephropathy
Type 2 Diabetes
Lead sponsor: University College Dublin
Sponsor class: OTHER
Collaborators: name: Irish Endocrine Society
name: Royal College of Physicians
name: Merck Sharp & Dohme LLC
name: Eli Lilly and Company
First posted: 2014-05-30
Enrollment: 17
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will be a prospective cohort study with 120 participants: 40 per group. I have calculated this sample size to achieve a 90% power based on a 50% reduction in urinary chemokines and circulating pro-inflammatory immune cells 1-4. This power calculation anticipates a 10% dropout rate.

Patients with DKD presenting to the diabetes service of St Vincent's University Hospital (SVUH) and Mater Misericordiae University Hospital (MMUH) who are commenced on GLP-1, DPP4i or insulin for the first time will be invited to participate in the study.

Brief summary: This study aims to determine if different diabetes treatments have different effects on inflammation; in particular, kidney inflammation. This type of inflammation is common in people with diabetes, and can lead to kidney failure. This study will investigate the effect of different types of diabetes treatment on kidney inflammation. This will help us to decide if certain types of medicine should be preferred in people with evidence of inflammation in their kidneys, as this may help prevent major complications including kidney failure.

Detailed description: In this prospective cohort study, patients who are clinically determined to require escalation of their glycaemic therapy, and prescribed a DPP4 inhibitor, GLP-1 receptor agonist, or insulin, will be invited to participate.

Blood and urine samples will be taken before, 4 to 8 weeks after, and 26 weeks after starting the new therapy. Markers of inflammation, renal function and glycemic control will be measured at each timepoint.

Eligibility criteria: Inclusion Criteria:

* Age over 30 years
* Diagnosis of type 2 diabetes for one year or more
* Diagnosis of DKD as defined by two distinct albumin:creatinine ratio measurements above the gender specific range in the local reference laboratory with an interval of no less than eight week between measurements
* Stable dose of an inhibitor of the renin angiotensin system for a period of 8 weeks

Exclusion Criteria:

* Any cognitive impediment that preclude the participant from giving free and informed consent
* Substance abuse including alcohol excess
* Use of a GLP-1 analogue in the last 6 months
* Pregnancy
* Hypersensitivity to the prescribed treatment

Primary outcomes:
measure: Monocyte:chemoattractant protein 1 (MCP-1):creatinine ratio
timeFrame: 6 months
Secondary outcomes:
measure: Albumin:creatinine ratio
timeFrame: 6 months
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
Study officials:
affiliation: University College Dublin
name: Donal O'Shea, MD FRCPI
role: STUDY_DIRECTOR
affiliation: University College Dublin
name: Carel W le Roux, PhD MB FRCP
role: STUDY_DIRECTOR
affiliation: University College Dublin
name: Mensud Hatunic, MD MRCPI
role: STUDY_DIRECTOR
References:
citation: Fenske WK, Dubb S, Bueter M, Seyfried F, Patel K, Tam FW, Frankel AH, le Roux CW. Effect of bariatric surgery-induced weight loss on renal and systemic inflammation and blood pressure: a 12-month prospective study. Surg Obes Relat Dis. 2013 Jul-Aug;9(4):559-68. doi: 10.1016/j.soard.2012.03.009. Epub 2012 Apr 10.
citation: Hogan AE, Gaoatswe G, Lynch L, Corrigan MA, Woods C, O'Connell J, O'Shea D. Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus. Diabetologia. 2014 Apr;57(4):781-4. doi: 10.1007/s00125-013-3145-0. Epub 2013 Dec 21.
citation: Hattori S. Sitagliptin reduces albuminuria in patients with type 2 diabetes. Endocr J. 2011;58(1):69-73. doi: 10.1507/endocrj.k10e-382. Epub 2010 Dec 28.
citation: Wu JD, Xu XH, Zhu J, Ding B, Du TX, Gao G, Mao XM, Ye L, Lee KO, Ma JH. Effect of exenatide on inflammatory and oxidative stress markers in patients with type 2 diabetes mellitus. Diabetes Technol Ther. 2011 Feb;13(2):143-8. doi: 10.1089/dia.2010.0048.