Intervention using vitamin D for elevated urinary albumin in type 2 diabetes mellitus (IDEAL-2 Study): study protocol for a randomised controlled trial

Shahrad Taheri, Muhammad Asim, Hassan Al Malki, Omar Fituri, Manikkam Suthanthiran, Phyllis August, IDEAL-2 Study Team, Muhammad Asim, Hassan Al-Malki, Omar Fituri, Awad Rachid, Abdelaziz Adel, Ahmed Hamdi, Awais Nauman, Gamal Farghaly, Mohamad Elkadi, Shahrad Taheri, Phyllis August, Manikkam Suthanthiran, Amin Jayyousi, Buthaina Ibrahim, Ibrahim Janahi, Robert Menzies, Seleena Farook, Salma Bashir, Odette Chagoury, Sopna Choudhury, Sherryl Payra, Omar Omar, Maria Pallayova, Sahar Agouba, Sally Elgazzar, Hadya Elshakh, Hoda Gad, Samah Chalil, Amany Dahir, Hiba Tohid, Subitha Chinnaiyan, Shahrad Taheri, Muhammad Asim, Hassan Al Malki, Omar Fituri, Manikkam Suthanthiran, Phyllis August, IDEAL-2 Study Team, Muhammad Asim, Hassan Al-Malki, Omar Fituri, Awad Rachid, Abdelaziz Adel, Ahmed Hamdi, Awais Nauman, Gamal Farghaly, Mohamad Elkadi, Shahrad Taheri, Phyllis August, Manikkam Suthanthiran, Amin Jayyousi, Buthaina Ibrahim, Ibrahim Janahi, Robert Menzies, Seleena Farook, Salma Bashir, Odette Chagoury, Sopna Choudhury, Sherryl Payra, Omar Omar, Maria Pallayova, Sahar Agouba, Sally Elgazzar, Hadya Elshakh, Hoda Gad, Samah Chalil, Amany Dahir, Hiba Tohid, Subitha Chinnaiyan

Abstract

Background: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is associated with serious macro- and microvascular complications. In particular, diabetic kidney disease (DKD), which begins with excessive urinary albumin excretion, has a significant impact on affected individuals and is costly to healthcare services. Inhibition of the renin-angiotensin-aldosterone system (RAAS) with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) significantly reduces albuminuria in diabetes, but this effect is not observed in all those treated. Active vitamin D analogues have been observed to be reno-protective through inhibition of RAAS in animal and human studies. Therefore, it can be hypothesised that an active vitamin D analogue will have an additional benefit to ACEI/ARB treatment for albuminuria reduction in DKD.

Methods: The planned study is an ongoing non-blinded randomised controlled parallel-group trial examining the impact, in individuals with T2DM, of the addition of bioactive vitamin D (calcitriol) to RAAS inhibition treatment using ACI or ARB on urinary albumin excretion over a period of 26 weeks. The primary outcome measure is the urinary albumin creatinine ratio. It is planned for the study to recruit 320 participants. Other outcome measures of interest include 24-h urine albumin (24 h UA) excretion, estimated glomerular filtration rate (eGFR), blood pressure and quality of life. Safety will be assessed throughout.

Discussion: If the addition of calcitriol to RAAS inhibition with ACEI or ARB safely results in a significant reduction in albuminuria, the study adds to the body of evidence supporting a role for vitamin D in reno-protection, will inform clinical practice and could result in significant reduction of healthcare costs associated with DKD.

Trial registration: ISRCTN, ISRCTN86739609 . Registered on 7 June 2017. ClinicalTrials.gov, NCT03216564 . Registered on 13 July 2017.

Keywords: Albuminuria; Angiotensin converting enzyme inhibitor; Angiotensin receptor blocker; Diabetic kidney disease; Type 2 diabetes mellitus; Vitamin D.

Conflict of interest statement

Ethics approval and consent to participate

Ethical approval for the study has been obtained from the Hamad Medical Corporation IRB (no. 16235/16), Weill Cornell Medicine – Qatar IRB (14–00039). All participants provide written informed consent.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
CONSORT flow chart for IDEAL-2 study
Fig. 2
Fig. 2
Schedule of enrolment, intervention, study visits and assessments for both study groups

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