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Metabolic Effects of the SGLT-2 Inhibitor Empagliflozin in Patients With Diabetic Nephropathy (MEDiaN) ((MEDiaN))

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03933956
Recruitment Status : Suspended (The study will be temporarily suspended due to the COVID-19 situation.)
First Posted : May 1, 2019
Last Update Posted : May 20, 2020
Sponsor:
Collaborator:
Duke-NUS Graduate Medical School
Information provided by (Responsible Party):
Singapore General Hospital

Brief Summary:

The MEDiaN study aims to examine the state of fuel metabolism in participants with diabetic nephropathy (DN) before and after the use of the sodium-glucose transport protein 2 inhibitor (SGLT-2i) empagliflozin. The goals of the MEDiaN study are to better understand the contribution of fuel metabolism to the development of DN, and to determine if changes to fuel metabolism can have a positive impact on this disease.

The MEDiaN study is a single-center single-arm open-label intervention study to examine the effects of empagliflozin 10mg daily taken for 30 days on fuel oxidation patterns in participants with type 2 diabetes and DN.


Condition or disease Intervention/treatment Phase
Diabetic Nephropathies Drug: Empagliflozin 10 MG Phase 3

Detailed Description:

Diabetic nephropathy (DN) is a common cause of end-stage renal disease. MEDiaN study investigators hypothesize that dysregulated mitochondrial fuel oxidation is a major driver of diabetic nephropathy. The sodium-glucose transport protein 2 inhibitor (SGLT-2i) empagliflozin has been shown to slow the progression of DN in patients with diabetes.

The MEDiaN study aims to examine the state of fuel metabolism in participants with DN before and after the use of the SGLT-2i empagliflozin. The goals of the MEDiaN study are to better understand the contribution of fuel metabolism to the development of DN, and to determine if changes to fuel metabolism can have a positive impact on this disease.

The MEDiaN study is a single-center single-arm open-label intervention study to examine the effects of empagliflozin 10mg daily taken for 30 days on fuel oxidation patterns in participants with type 2 diabetes and DN.

The MEDiaN study plans to recruit 40 participants aged 21 to 100 years of age with type 2 diabetes mellitus and diabetic nephropathy. Participants will receive treatment with oral empagliflozin 10mg daily for 30 days. The state of fuel metabolism will be examined through metabolomics analysis of blood and urine samples before and after empagliflozin 10mg daily taken for 30 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single-arm open-label intervention study
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Metabolic Effects of the SGLT-2 Inhibitor Empagliflozin in Patients With Diabetic Nephropathy (MEDiaN)
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : August 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Empagliflozin-treated
Oral empagliflozin tablets 10mg daily, taken for 30 days.
Drug: Empagliflozin 10 MG
Oral empagliflozin 10mg daily for 30 days
Other Name: Jardiance




Primary Outcome Measures :
  1. Change in lipid metabolome signature [ Time Frame: Baseline and after 30 days of treatment with empagliflozin 10mg daily ]
    Change in lipid metabolome signature following 30 days of empagliflozin treatment

  2. Change in ketone signature [ Time Frame: Baseline and after 30 days of treatment with empagliflozin 10mg daily ]
    Change in ketone signature following 30 days of empagliflozin treatment

  3. Change in amino acid metabolome signature [ Time Frame: Baseline and after 30 days of treatment with empagliflozin 10mg daily ]
    Change in amino acid metabolome signature following 30 days of empagliflozin treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Man or woman between 21 and 100 years of age
  2. Type 2 diabetes mellitus as defined by:

    • Fasting plasma glucose ≥7.0mmol/l, or
    • Symptoms of hyperglycemia with casual plasma glucose ≥11.1 mmol/L, or
    • 2-hour plasma glucose ≥11.1 mmol/l after a 75-gram oral glucose load, or
    • Known type 2 diabetes mellitus diagnosed by a medical practitioner
  3. Two or more measurements indicating increased urine protein excretion within 1-year

    Increased urine protein excretion is defined as:

    • Urine microalbumin/creatinine ratio (ACR) > 3.3 mg/mmol creatinine or
    • Urine total protein/creatinine ratio (PCR) > 0.2 g/urine creatinine
  4. Known diabetes duration > 3 months
  5. HbA1c ≤9% (within 3 months prior to enrolment)
  6. Not currently treated with an SGLT-2 inhibitor, and have not received SGLT-2 inhibitor therapy within the last 10 weeks.
  7. Stable diabetes therapy for at least 3months as defined as:

    • No increase in dose of diabetes medications by more than two-fold or
    • No new agents added within the previous 3 months
  8. Stable doses of angiotensin converting enzyme (ACE) inhibitors or angiotensin AT(1)-receptor blockers (ARBs) for at least 3 months.
  9. Capable of providing informed consent

Exclusion Criteria:

  1. Type 1 diabetes mellitus
  2. Ketosis-prone diabetes
  3. Previous diabetic ketoacidosis
  4. History of Fournier's gangrene or skin and soft tissue infections of the perineum
  5. Recurrent or severe urinary tract or genital mycotic infections, or history of genitourinary infection within 2 weeks prior to informed consent
  6. Significant renal impairment (estimated Glomerular Filtration Rate < 45 ml/min/1.73m2**)
  7. Dialysis or kidney transplant
  8. Renal artery stenosis
  9. Alanine aminotransferase or aspartate aminotransferase above 3x upper limit of normal
  10. Significant change in weight (≥10% in the preceding 6 months)
  11. Treatment with anti-obesity drugs
  12. Previous bariatric surgery or other gastrointestinal surgeries that induce chronic malabsorption
  13. Treatment with systemic glucocorticoids
  14. Blood dyscrasias or clinically significant anaemia (Haemoglobin < 10 g/L)
  15. Medical condition likely to limit survival to less than 3 years
  16. Uncontrolled thyrotoxicosis, untreated hypothyroidism
  17. Any ongoing acute medical illnesses
  18. Hospitalization within 1 month prior to enrolment
  19. Nursing mothers
  20. Pregnancy, currently trying to become pregnant, or of child-bearing potential and not practicing an acceptable method of birth control or do not plan to continue using this method throughout the study
  21. Excessive alcohol intake (> 1 unit per day for women and > 2 units per day for men)
  22. History of drug abuse
  23. Pancreatic insulin deficiency from any cause (history of pancreatitis, pancreatic surgery)
  24. Known intolerance or allergic reactions to empagliflozin or other SGLT-2 inhibitors
  25. Current participation in another clinical trial, or ingestion of investigational drug in another trial within 30 days prior to enrolment.
  26. Presence of any non-DN renal glomerular disease (e.g. IgA nephropathy, lupus nephritis, membranous glomerulonephritis, focal segmental glomerular sclerosis)
  27. Any previous organ transplantation
  28. Any factors likely to limit adherence to interventions (e.g. dementia; alcohol or substance abuse; history of unreliability in medication taking or appointment keeping; significant concerns about participation in the study from spouse, significant other or family members)
  29. Failure to obtain informed consent from participant
  30. Presence of postural hypotension or clinically significant dehydration (reduced skin turgor, dry oral mucosa, hypotension)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03933956


Locations
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Singapore
Singapore General Hospital
Singapore, Singapore, 169608
Sponsors and Collaborators
Singapore General Hospital
Duke-NUS Graduate Medical School
Investigators
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Principal Investigator: Yun Rui Amanda Lam, MBBS MRCP Singapore General Hospital
  Study Documents (Full-Text)

Documents provided by Singapore General Hospital:
Study Protocol  [PDF] December 9, 2018

Publications:

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Responsible Party: Singapore General Hospital
ClinicalTrials.gov Identifier: NCT03933956    
Other Study ID Numbers: MEDiaN2018
Duke-NUS-TIDR/2018/0010 ( Other Grant/Funding Number: Tanoto Initiative for Diabetes Research Award )
First Posted: May 1, 2019    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Singapore General Hospital:
Diabetic nephropathy
Sodium-glucose Cotransporter 2 Inhibitors
Additional relevant MeSH terms:
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Kidney Diseases
Diabetic Nephropathies
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Empagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs