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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by The Nazareth Hospital, Israel.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Western Galilee Hospital-Nahariya
Information provided by (Responsible Party):
The Nazareth Hospital, The Nazareth Hospital, Israel
ClinicalTrials.gov Identifier:
NCT01566006
First received: November 15, 2010
Last updated: March 28, 2012
Last verified: March 2012

November 15, 2010
March 28, 2012
April 2012
June 2013   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
16 time points over 1 year.
Same as current
Complete list of historical versions of study NCT01566006 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Mycophenolate Mofetil, Carnitine and PDE5 Inhibitor, Three Potential Treatments for Resistant Proteinuria Slowing Diabetic Nephropathy Deterioration
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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Diabetic Nephropathy
  • Chronic Kidney Disease
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
  • No Intervention: control group
    group receiving the conventional treatment for DN
    Intervention: Drug: Mycophenolate Mofetil (MMF) ,phosphodiesterase 5 inhibitors , CARNITINE
  • Experimental: cellcept group
    additional to the conventional treatment patients will receive cellcept
    Intervention: Drug: Mycophenolate Mofetil (MMF) ,phosphodiesterase 5 inhibitors , CARNITINE
  • Experimental: carnitine group
    aside to the conventional treatment patients will receive carnitine
    Intervention: Drug: Mycophenolate Mofetil (MMF) ,phosphodiesterase 5 inhibitors , CARNITINE
  • Experimental: PDE5 group
    aside to the conventional treatment patients will receive PDE5 inhibitor
    Intervention: Drug: Mycophenolate Mofetil (MMF) ,phosphodiesterase 5 inhibitors , CARNITINE
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
80
August 2013
June 2013   (final data collection date for primary outcome measure)

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.
Both
30 Years to 80 Years
No
Contact: najla hamati 04-6028888 nana@nazhosp.com
Israel
 
NCT01566006
nazh8827ctil
Yes
The Nazareth Hospital, The Nazareth Hospital, Israel
The Nazareth Hospital, Israel
Western Galilee Hospital-Nahariya
Principal Investigator: Zaher Armaly, MD Nazareth Hospital (E.M.M.S)
The Nazareth Hospital, Israel
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP