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
  Purpose

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.


Condition Intervention
Diabetic Nephropathy
Chronic Kidney Disease
Drug: Mycophenolate Mofetil (MMF) ,phosphodiesterase 5 inhibitors , CARNITINE

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by The Nazareth Hospital, Israel:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 80
Study Start Date: April 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01566006

Contacts
Contact: najla hamati 04-6028888 nana@nazhosp.com

Locations
Israel
Nazareth hospital (EMMS) Not yet recruiting
Nazareth, Israel
Contact: Zaher Armaly, MD       zaherarmaly@nazhosp.com   
Sponsors and Collaborators
The Nazareth Hospital, Israel
Western Galilee Hospital-Nahariya
Investigators
Principal Investigator: Zaher Armaly, MD Nazareth Hospital (E.M.M.S)
  More Information

No publications provided

Responsible Party: The Nazareth Hospital, Zaher armaly , M.D, Head of Nephrology Department, The Nazareth Hospital, Israel, The Nazareth Hospital, Israel
ClinicalTrials.gov Identifier: NCT01566006     History of Changes
Other Study ID Numbers: nazh8827ctil
Study First Received: November 15, 2010
Last Updated: March 28, 2012
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by The Nazareth Hospital, Israel:
Mycophenolate mofetil (MMF)
Diabetic Nephropathy
proteinuria
Diabetic Nephropathy in Chronic Kidney Disease patients stages 2-4

Additional relevant MeSH terms:
Diabetic Nephropathies
Diabetes Mellitus, Type 2
Kidney Diseases
Proteinuria
Renal Insufficiency, Chronic
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Urologic Diseases
Diabetes Complications
Urination Disorders
Urological Manifestations
Signs and Symptoms
Renal Insufficiency
Carnitine
Mycophenolate mofetil
Mycophenolic Acid
Phosphodiesterase 5 Inhibitors
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on August 28, 2014