Environmental Exposure to Lead and Progressive Renal Insufficiency in Type II Diabetic Nephropathy
Information source: Chang Gung Memorial Hospital
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetic Nephropathies; Diabetes Mellitus, Type II
Intervention: EDTA chelating agents (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Chang Gung Memorial Hospital Official(s) and/or principal investigator(s):
Ja-Liang Lin, M.D., Principal Investigator, Affiliation: Chang Gung Memorial Hospital, Lin-Kou Medical Center
Overall contact:
Ja-Liang Lin, M.D., Phone: 886-3-3281200, Ext: 8181, Email: jllin@adm,cgmh.org.tw
Summary
Background The relationship between long-term heavy lead exposure and chronic interstitial
nephropathy is well recognized in the previous literatures. Several epidemiological studies
have demonstrated a positive association between blood lead levels and the age related
decreases of renal function in the general population and suggested that environmental
low-level lead exposure may accelerate the progression of renal function in the healthy
persons. In addition, previous our works suggest environmental lead exposure may correlate to
progressive renal insufficiency and lead chelation therapy or repeated lead chelation may
improve and slow the progressive renal insufficiency in non-diabetic patients with chronic
renal diseases. However, Diabetes mellitus is increasing in prevalence worldwide and is
currently estimated to affect more than 6. 5 percent of the population of the United States.
In addition, diabetes is the most common cause of end-stage renal disease in many countries,
accounting for about 40 percent of cases. It is still unknown that the relationship between
long-term environmental lead exposure and the progressive renal insufficiency in patients
with type II diabetes and diabetic nephropathy.
Methods One hundred and two patients with type II diabetes and diabetic nephropathy (serum
creatinine levels between 1. 5 mg per deciliter and 3. 9 mg per deciliter) who have a normal
body lead burden and no history of exposure to lead or other metals will be observed for 24
months. Then, about 60 subjects with high normal body lead burdens (at least 80 μg but less
than 600 μg) will be randomly assigned to the study and control groups. For three months, the
30 patients in the study group willvreceive lead-chelation therapy with calcium disodium EDTA
weekly until the body lead burden fallsl below 60 μg, and the 30 control group receive weekly
placebo. During the ensuing 24 months, the renal function will be regularly followed up every
3 months and EDTA mobilization tests will be assessed every 6 months. If body lead burden of
the study group patients increase more than 60μg, the chelation therapy will be performed
again until their body burden are less than 60 μg. The primary end point is an increase in
the serum creatinine level to 1. 5 times the base-line value during the observation period. A
secondary end point is the change in renal function during the follow up period.
Clinical Details
Official title: Environmental Lead Exposure and Progressive Renal Insufficiency in Patients With Type II Diabetes and Diabetic Nephropathy
Study design: Treatment, Randomized, Single Blind, Placebo Control, Parallel Assignment, Efficacy Study
Primary outcome: The primary end point is an increase in serum creatinine to 1.5 times the base-line value, measured on two occasions one month apart, or the need for hemodialysis during the longitudinal observation period.
Secondary outcome: A secondary end point is a temporal change in the creatinine clearance or glomerular filtration rate during the follow-up period.
Eligibility
Minimum age: 20 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Patients from 20 through 80 years of age who have type II diabetes mellitus with
diabetic nephropathy and followed up at our hospital for more than one year were
eligible if they have a serum creatinine concentration between 1. 5 mg per deciliter
(132. 6 μmol per liter) and 3. 9 mg per deciliter (344. 8 μmol per liter), with a daily
proteinuria more than 0. 5g/day and no micro-hematuria in urinalysis tests, normal size
of both kidneys, retinopathy with laser therapy by ophthalmologists, a history of
diabetes more than 5 years and no known history of exposure to lead or other heavy
metals (body lead burden, less than 600 μg [2. 90 μmol], as measured by EDTA
mobilization testing and 72-hour urine collection). Diabetic nephropathy diagnoses are
based on the patients’ history and the results of laboratory evaluations, renal
imaging, and renal histological examination.
Exclusion Criteria:
- type I diabetes; renal insufficiency with a potentially reversible cause, such as
malignant hypertension, urinary tract infection, hypercalcemia, or drug-induced
nephrotoxic effects; other systemic diseases, such as connective-tissue diseases; use
of drugs that may alter the course of renal disease, such as non-steroidal
anti-inflammatory agents, steroids, immunosuppressive drugs or Chinese herb drugs.;
previous marked exposure to lead (lead poisoning or occupational exposure); drug
allergies; and absence of informed consent.
Locations and Contacts
Ja-Liang Lin, M.D., Phone: 886-3-3281200, Ext: 8181, Email: jllin@adm,cgmh.org.tw
Chang Gung Memorial Hospital, Lin-Kou Medical Center, Taipei, Taiwan 105, China; Recruiting
Miin-Fu Chen, M.D., Phone: 886-3-3281200, Ext: 3672, Email: ysc3219@adm.cgmh.org.tw
Ja-Liang Lin, M.D., Principal Investigator
Yi-Rung Li, MD, Sub-Investigator
Dan-Tzu Lin-Tan, R.N., Sub-Investigator
Additional Information
Starting date: August 2005
Last updated: May 4, 2007
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