An Intervention to Examine the Effect of Vitamin D on Urine Protein Levels in Type 2 Diabetes (IDEAL-2)

Intervention Using Vitamin D for Elevated Urinary ALbumin in Diabetes (IDEAL-2)

Diabetic kidney disease (nephropathy) develops in nearly 40% of patients with type 2 diabetes mellitus. Diabetic nephropathy is caused by damage to the small blood vessels in the kidneys due to uncontrolled blood sugar levels, which mean that the kidneys become less effective at filtering urine. This is associated with albuminuria (protein in the urine). Treatment with some drugs reduces the loss of albumin through the urine and delays disease progression. There is increasing evidence that vitamin D could also be important in management of diabetic kidney disease. The aim of this study is to investigate the efficacy and safety of a combined regimen of calcitriol (active vitamin D) and established drugs for diabetic kidney disease.

Study Overview

• Status: Unknown
• Conditions: Diabetic Nephropathies
• Intervention / Treatment: Drug: Calcitriol

Detailed Description

The investigators propose to test the efficacy and safety of a combined regimen of calcitriol and angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in type 2 diabetes subjects with albuminuria. In the proposed study, the bioactive form of vitamin D (calcitriol) is being used for its ability to synergize with ACEI or ARB and prevent renal disease progression. The study expands on preliminary studies demonstrating a reduction in proteinuria with vitamin D analogue treatment, in subjects with both diabetic as well as non-diabetic kidney disease.

• Study Type: Interventional
• Enrollment (Anticipated): 320
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shahrad Taheri, MB BS PhD; Phone Number: 0097444928998; Email: szt2004@qatar-med.cornell.edu
• Study Contact Backup: Name: Muhammad Asim, MB BS; Phone Number: 0097455838342; Email: Masim@hamad.qa

Study Locations

• Qatar
  • Doha, Qatar
    • Recruiting
    • Hamad Medical Corporation
    • Contact: Muhammad Asim, MB BS; Phone Number: 0097455838342; Email: Masim@hamad.qa
    • Principal Investigator: Muhammad Asim, MB BS
    • Principal Investigator: Shahrad Taheri, MB BS PhD
    • Principal Investigator: Phyllis August, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age greater than or equal to 18 years and less than 80 years
2. Diagnosis of T2DM requiring treatment with at least one oral hypoglycaemic medication or insulin 2.1. Subjects will be considered to have established T2DM if the diagnosis of diabetes has been made and the subjects were treated with insulin or an oral hypoglycaemic agent for at least 6 months after diagnosis 2.2. Subjects will be considered to have newly established T2DM if the diagnosis of diabetes was diagnosed with a fasting plasma glucose ≥ 7 mmol/L (126 mg/dL) or haemoglobin A1c is >6.5% in the past 6 months

3. Documented albuminuria defined as a presence of albuminuria on two occasions in the last six months:

   3.1. Albumin ≥ 30 mg/24 hour in a 24 hour urine collection, or 3.2. Albumin ≥ 20 μg/min in a short-time urine collection, or 3.3. Albumin ≥ 30 mg/L in a spot urine sample, or 3.4. A spot-urine albumin-creatinine ration (ACR) ≥ 30 mg/g creatinine (≥ 2.5 mg/mmol creatinine in men, ≥ 3.5 mg/mmol creatinine in women)

4. Estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Renal Disease (MDRD) equation of ≥ 25 mL/min/1.73 m2

Exclusion Criteria:

1. If female, positive pregnancy test or planning pregnancy in the subsequent 12 months
2. Pregnant
3. Breastfeeding
4. Corrected serum calcium ≥ 2.62 mmol/L
5. Serum Potassium > 5.2 mmol/L if not on ACEI or ARB; Serum Potassium > 6.0 mmol/L if on ACEI or ARB
6. 25-hydroxyvitamin D (25-OH Vit D) > 80 ng/mL
7. PTH > 200 pg/mL
8. Poorly controlled hypertension defined as systolic blood pressure ≥ 180 mm Hg or diastolic blood pressure ≥ 110 mm Hg
9. Systolic blood pressure (SBP) ≤ 110 mm Hg
10. History of kidney stones
11. History of severe chronic disease (e.g. chronic liver disease)
12. Active malignancy
13. Recent diagnosis of acute renal failure within 3 months of screening visit
14. Likelihood of renal replacement therapy within 1 year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Participants are treated with angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) AND active vitamin D (Calcitriol) 0.25 micrograms orally per day for 26 weeks.	Drug: Calcitriol; Active vitamin D (Calcitriol) 0.25 micrograms; Other Names: Active Vitamin D
No Intervention: Usual Care; Participants are treated with ACEI/ARB alone for 26 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary albumin creatinine ratio (ACR) measured biochemically	Urine albumin and creatinine will be measured biochemically and their ratio calculated	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour urine albumin (24h UA) excretion	24-hour urine albumin (24h UA) excretion measured biochemically	26 weeks
Estimated glomerular filtration rate (eGFR)	Calculated using the Modification of Diet in Renal Disease (MDRD) equation	26 weeks
Blood pressure	Blood pressure measured using a digital sphygmomanometer	26 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Reported Outcome: Quality of life	Measured using the EQ5D questionnaire	26 weeks

Collaborators and Investigators

• Sponsor: Hamad Medical Corporation
• Collaborators: Weill Cornell Medical College in Qatar
• Investigators: Principal Investigator: Muhammad Asim, MB BS, Hamad Medical Corporation

Publications and helpful links

General Publications

• Taheri S, Asim M, Al Malki H, Fituri O, Suthanthiran M, August P; IDEAL-2 Study Team. Intervention using vitamin D for elevated urinary albumin in type 2 diabetes mellitus (IDEAL-2 Study): study protocol for a randomised controlled trial. Trials. 2018 Apr 17;19(1):230. doi: 10.1186/s13063-018-2616-5.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2017
• Primary Completion (Anticipated): May 10, 2019
• Study Completion (Anticipated): May 10, 2019

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: July 11, 2017
• First Posted (Actual): July 13, 2017

Study Record Updates

• Last Update Posted (Actual): September 6, 2018
• Last Update Submitted That Met QC Criteria: September 4, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Vitamin D; Calcitriol
• Other Study ID Numbers: 16235/16; 1400039 (Other Identifier: Weill Cornell Medicine - Qatar)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: For data, please contact investigators

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No