Mycophenolate Mofetil, Carnitine and PDE5 Inhibitor, Three Potential Treatments for Resistant Proteinuria Slowing Diabetic Nephropathy Deterioration (Myridian)

March 28, 2012 updated by: The Nazareth Hospital, The Nazareth Hospital, Israel

Mycophenolate Mofetil (MMF) ,Carnitine and Phosphodiesterase Type 5 Inhibitor, Three Potential Treatments for Resistant Proteinuria and for Slowing the Deterioration of Diabetic Nephropathy in Patients With Type II Diabetes Mellitus

Diabetes mellitus (DM) is a growing disease and it is a public health concern, and projections of its future effect are alarming. About one third of those affected will develop diabetic nephropathy at 20 years after diagnosis. Of these patients, 20% will develop clinically end-stage renal disease ESRD, requiring renal replacement therapy (RRT). Patients with type 2 diabetes account for most patients with end stage renal disease (ESRD) and RRT.

To the best of the investigators knowledge, the effects of MMF on diabetic nephropathy in patients with DM type II were not studied so far. Therefore, the purpose of this pilot study is to evaluate the effects of Mofetil Mycophenolate (MMF) on proteinuria and progression of kidney disease of diabetic origin, in patients at high risk for progressive renal failure in whom other treatment modalities are insufficient or had failed.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The pathophysiology of the diabetic nephropathy was initially considered to be merely secondary to a non-immune mechanism, specifically due to metabolic (hyperglycemia) and hemodynamic (glomerular capillary hypertension - mechanical stretching) factors. However, our understanding of the pathophysiological processes that lead to diabetic nephropathy and its progression is now clearer and involved not only a non immune mechanism, but also immune-mediated and inflammatory mechanism. Activation of the immune system, with the participation of a chronic inflammatory state, plays a central role in the pathogenesis of diabetic nephropathy. Evidence for the involvement of the immune system in the pathogenesis of diabetic nephropathy was derived from the elevated levels of proinflammatory cytokines such as IL-1, IL-6, IL-18, and TNF-α. These factors are important predictors of the development of diabetic nephropathy, and recently it was shown that these inflammatory cytokines play a determinant role in the development and progression of the microvascular diabetic nephropathy. The first published study that showed the implication of the inflammatory cytokines in the pathogenesis of the diabetic nephropathy was in 1991. Mycophenolate Mofetil (MMF) is an immunosuppressant drug, used to prevent rejection, especially acute rejection in various organ transplantations, mainly kidney transplantation since 1995. In the last decade there are increasing reports describing the beneficial use of MMF in immune- mediated and auto-immune disorders such as Systemic Lupus Erythematosus, IGA nephropathy and other glomerulopathies.

Unfortunately, the potentially beneficial effects of MMF on diabetic nephropathy were not examined in clinical DM and is limited to diabetic rats. In a recent study, Utimura et al. have demonstrated that MMF largely prevented the development of albuminuria and glomerular injury in experimental diabetic nephropathy. The beneficial effect of MMF was not related to its action on glomerular hemodynamic or improvement of metabolic control, but probably related directly to its immunosuppressive and anti-inflammatory properties.

Study Type

Interventional

Enrollment (Anticipated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Nazareth, Israel
        • Nazareth hospital (EMMS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. T2 DM at age ≥18 y with at least 10 years duration of diabetes.
  2. Proteinuria due to diabetic nephropathy of ≥ 2 gram/d treated with ACEi or ARBs at maximal tolerated dose or both of them.
  3. CKD grade 1-3
  4. Diabetic retinopathy (discuss with Zaid)

Exclusion Criteria:

  1. Proteinuria of non diabetic origin
  2. Overlap Proteinuria with diabetic nephropathy
  3. Other intercurrent illness (fever due to infection ….) that can interfere with the urine protein secretion.
  4. Acute Kidney Injury.
  5. CKD stage 4-5.
  6. New renoprotective treatment in the last 6 months before enrollment.
  7. Changes in dosage of one of the renoprotective drugs in the last 6 months before enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: control group
group receiving the conventional treatment for DN
Drug: Mycophenolate Mofetil (MMF) ,phosphodiesterase 5 inhibitors , CARNITINE
effect of MMF on diabetic nephropathy patients by evaluating its effect on proteinuria and progression of kidney disease of diabetic origin
Experimental: cellcept group
additional to the conventional treatment patients will receive cellcept
Drug: Mycophenolate Mofetil (MMF) ,phosphodiesterase 5 inhibitors , CARNITINE
effect of MMF on diabetic nephropathy patients by evaluating its effect on proteinuria and progression of kidney disease of diabetic origin
Experimental: carnitine group
aside to the conventional treatment patients will receive carnitine
Drug: Mycophenolate Mofetil (MMF) ,phosphodiesterase 5 inhibitors , CARNITINE
effect of MMF on diabetic nephropathy patients by evaluating its effect on proteinuria and progression of kidney disease of diabetic origin
Experimental: PDE5 group
aside to the conventional treatment patients will receive PDE5 inhibitor
Drug: Mycophenolate Mofetil (MMF) ,phosphodiesterase 5 inhibitors , CARNITINE
effect of MMF on diabetic nephropathy patients by evaluating its effect on proteinuria and progression of kidney disease of diabetic origin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
proteinuria
Time Frame: before beginging of the treatment - baseline, after 1,2,3,4 weeks, after 1,2,3,4,5,6,7,8,9,10,11,12 months of the beginning of the treatment
16 time points over 1 year.
before beginging of the treatment - baseline, after 1,2,3,4 weeks, after 1,2,3,4,5,6,7,8,9,10,11,12 months of the beginning of the treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Nazareth Hospital, Israel

Collaborators

Western Galilee Hospital-Nahariya

Investigators

  • Principal Investigator: Zaher Armaly, MD, Nazareth Hospital (E.M.M.S)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Anticipated)

June 1, 2013

Study Completion (Anticipated)

August 1, 2013

Study Registration Dates

First Submitted

November 15, 2010

First Submitted That Met QC Criteria

March 28, 2012

First Posted (Estimate)

March 29, 2012

Study Record Updates

Last Update Posted (Estimate)

March 29, 2012

Last Update Submitted That Met QC Criteria

March 28, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • nazh8827ctil

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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