Mycophenylate Mofetil and Tacrolimus Versus Tacrolimus for the Treatment of Idiopathic Membranous Glomerulonephritis (IMG) - Full Text View

Sponsor:	Imperial College Healthcare NHS Trust
Information provided by:	Imperial College Healthcare NHS Trust
ClinicalTrials.gov Identifier:	NCT00843856

Purpose

Membranous nephropathy is a common cause of nephrotic syndrome in adults. It is difficult to treat and if persistent leads to end stage renal failure in a significant number of patients. It is currently treated in this institution with tacrolimus monotherapy. This is effective in the majority of patients in reducing proteinuria but the remissions are often partial and patients tend to relapse when the tacrolimus treatment is stopped. We propose to use mycophenylate mofetil in combination with tacrolimus with the aim of obtaining a more complete initial response to treatment, a decreased rate of relapse on withdrawal of therapy and less progression of renal failure. This will be a randomised control trial, patients will be randomised to receive treatment with tacrolimus alone (our current standard therapy)or treatment with tacrolimus and mycophenylate mofetil. Participants will receive treatment for up to 2 years and then be monitored for relapse of their nephrotic syndrome.

Study Hypothesis: When Mycophenylate mofetil is added to tacrolimus in the treatment of membranous glomerulonephritis it is likely to improve the initial response to treatment and reduce the risk of relapse on stopping therapy.

Condition	Intervention	Phase
Nephrotic Syndrome Secondary to Idiopathic Membranous Glomerulonephritis	Drug: tacrolimus Drug: tacrloimus and mycophenylate mofetil	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Mycophenylate Mofetil and Tacrolimus vs Tacrolimus Alone for the Treatment of Idiopathic Membranous Glomerulonephritis

Resource links provided by NLM:

Drug Information available for: Tacrolimus anhydrous Tacrolimus

U.S. FDA Resources

Further study details as provided by Imperial College Healthcare NHS Trust:

Primary Outcome Measures:

Efficacy of MMF in preventing relapse of nephrotic syndrome secondary to membranous glomerulonephritis on withdrawal of tacrolimus therapy. This will be initially measured at 6 months post withdrawal of tacrolimus therapy. [ Time Frame: 6 months post withdrawl or tacrolimus therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The time to obtaining remission from proteinuria The degree of remission of proteinuria obtained (complete or partial) The rate of decline of renal function measured by the MDRD equation for glomerular filtration rate [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	32
Study Start Date:	February 2009
Estimated Study Completion Date:	February 2014
Estimated Primary Completion Date:	February 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
tacrolimus: Active Comparator Intervention type -drug tacrolimus therapy 2mg bd adjust to obtain levels of 5-12ng/L	Drug: tacrolimus tacrolimus 2mgs bd adjusted to obtain levels of 5-12ng/ml
tacrolimus and mycophenylate mofetil: Active Comparator tacrolimus 2mgs bd (adjusted to obtain levels 5-12mg/L and mycophenylate mofetil 500mg bd adjusted to obtain levels 1.5-3mg/L	Drug: tacrloimus and mycophenylate mofetil tacrolimus 2mg bd adjusted to achieve levels of 5-12ng/L mycophenylate mofetil 500mgs bd adjusted to achieve levels of 1.5-3mg/L

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Idiopathic membranous glomeulonephritis on renal biopsy
Proteinura - protein/creatinine ratio (PCR) > 100 units with hypoalbuminaemia or PCR > 300 units with normal serum albumin despite 3 months treatment with maximum tolerated doses of ace inhibitors and angiotensin 2 antagonists (or shorter if life threatening complications of nephrotic syndrome require institution of immediate immunosuppression)
Male or female patients aged 18 to 80 years

Exclusion Criteria:

Hepatits B hepatitis C or HIV positive
Malignancy (all patients must have a CT chest abdomen and pelvis and other investigations if clinically indicated)
Untreated infection
Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception
Any condition judged by the investigator that would cause the study to be detrimental to the patient

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00843856

Locations

United Kingdom
Hammersmith Hospital	Recruiting
London, United Kingdom, W12 OHS
Contact: Megan E Griffith, MBChB (hons)PhD 02083835272 megan.griffith@imperial.nhs.uk
Contact: Tom D Cairns 02083835272 tom.cairns@nhs.net
Principal Investigator: Dr M Griffith, MBChB PhD

Sponsors and Collaborators

Imperial College Healthcare NHS Trust

More Information

No publications provided

Responsible Party:	Imperial College Healthcare NHS Trust, Hammersmith Site ( Dr Rodney Gale )
Study ID Numbers:	2008-001009-41, EUDRACT Number 2008-001009-41
Study First Received:	February 12, 2009
Last Updated:	October 2, 2009
ClinicalTrials.gov Identifier:	NCT00843856 History of Changes
Health Authority:	United Kingdom: National Health Service

Additional relevant MeSH terms:

Glomerulonephritis
Autoimmune Diseases
Disease
Immunologic Factors
Immune System Diseases
Physiological Effects of Drugs
Glomerulonephritis, Membranous
Tacrolimus
Immunosuppressive Agents

Pharmacologic Actions
Nephrosis
Pathologic Processes
Urologic Diseases
Syndrome
Nephritis
Kidney Diseases
Nephrotic Syndrome

ClinicalTrials.gov processed this record on February 08, 2010