IgA Nephropathy
Conditions
Keywords
Proteinuria, Immunoglobulin A
Brief summary
IgA nephropathy (IgAN) is the most common type of glomerulonephritis worldwide. 15-40% of individuals diagnosed with IgAN, including children, will eventually progress to chronic renal insufficiency (CRI) and end stage renal disease (ESRD). The study is to evaluate the safety and benefits of MMF in patients with IgAN who have been pre-treated (and continue to be treated) with angiotensin converting enzyme inhibitors (ACEi) and fish oil supplements (FOS).
Detailed description
A multi-center, randomized, controlled clinical trial to test the hypothesis that treatment with mycophenolate mofetil (MMF) will lead to significant and sustained improvement in proteinuria in patients with IgA Nephropathy who have been pre-treated (and continue to be treated) with ACEi and FOS compared to a placebo control group of patients receiving comparable doses of ACEi and FOS without MMF. Data for this outcome will be examined every six months and at the end of 2 years of study. Comparisons will be made between the two treatment groups for change from entry level in urine protein to creatinine (UPr/Cr) ratio, 24-hour urine protein excretion rate and estimated glomerular filtration rate (GFR).
Interventions
Sponsors
St. Joseph's Hospital and Medical Center, Phoenix
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients ages 7-70 years old * Renal biopsy, diagnostic for IgA nephropathy * Must be able to take oral medication
Exclusion criteria
* Clinical and histologic evidence of systemic lupus erythematosus * Well-documented history of Henoch-Schonlein purpura. * Clinical evidence of cirrhosis or chronic liver disease * Abnormal laboratory values at the time of study entry * Estimated GFR outside of protocol defined limits * History of significant gastrointestinal disorder * Active systemic infection or history of serious infection within one month of entry or known infection with HIV, hepatitis B, or hepatitis C. * Other major organ system disease or malignancy * Current or prior treatment with MMF or azathioprine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Proteinuria - Uprotein/Creatinine Ratio | Plan was to measure uprotein/creatinine ratio for 12 months on MMF or placebo, and then 12 months post-treatment. Data given after 6 months MMF/placebo. | Urine protein/creatinine ratio after 6 months treatment with MMF or placebo. |
Secondary
| Measure | Time frame |
|---|---|
| Change in Estimated Glomerular Filtration Rate (GFR) to Less Than 60% of the Baseline Level | 12 months |
Countries
United States
Participant flow
Recruitment details
184 subjects were enrolled. 146 subjects completed entry evaluation. 97 subjects fulfilled entry criteria and were started on 3 month course of Omacor and lisinopril. 94 subjects completed the 3 months of treatment.
Pre-assignment details
After the 3 months, 58 subjects fulfilled criteria for going into the MMF vs. placebo phase. Six of the 58 subjects were not randomized because the External Advisory Committee/Data Safety Monitoring Board recommended stopping the trial because of lack of effect.
Participants by arm
| Arm | Count |
|---|---|
| Mycophenolate Mofetil (MMF) Subjects receive ACEi, FOS, and MMF. Dose is based on body size (between 25mg/kg/day and 36mg/kg/day with a maximum dose 1gm BID; initial dose to be used in the first 2 weeks of therapy will be approximately 1/2-2/3 of the full dose). Route of administration is oral. Frequency is daily. MMF will be administered up to 12 months.
Mycophenolate Mofetil (MMF) | 25 |
| Placebo Subjects receive ACEi and FOS and placebo. | 27 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Fall in GFR | 3 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Post-therapy hyperflycemia | 0 | 1 |
| Overall Study | Pregnancy | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Trial terminated | 10 | 7 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Mycophenolate Mofetil (MMF) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 21 Participants | 41 Participants |
| Age, Continuous | 31.8 years STANDARD_DEVIATION 11.7 | 32.2 years STANDARD_DEVIATION 13.2 | 32.0 years STANDARD_DEVIATION 12.2 |
| Region of Enrollment Canada | 6 participants | 4 participants | 10 participants |
| Region of Enrollment United States | 19 participants | 23 participants | 42 participants |
| Sex: Female, Male Female | 11 Participants | 9 Participants | 20 Participants |
| Sex: Female, Male Male | 14 Participants | 18 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 25 | 27 / 27 |
| serious Total, serious adverse events | 1 / 25 | 1 / 27 |
Outcome results
Primary
Change in Proteinuria - Uprotein/Creatinine Ratio
Urine protein/creatinine ratio after 6 months treatment with MMF or placebo.
Time frame: Plan was to measure uprotein/creatinine ratio for 12 months on MMF or placebo, and then 12 months post-treatment. Data given after 6 months MMF/placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mycophenolate Mofetil (MMF) | Change in Proteinuria - Uprotein/Creatinine Ratio | 1.40 ratio | Standard Deviation 0.72 |
| Placebo | Change in Proteinuria - Uprotein/Creatinine Ratio | 1.58 ratio | Standard Deviation 1.07 |
Secondary
Change in Estimated Glomerular Filtration Rate (GFR) to Less Than 60% of the Baseline Level
Time frame: 12 months