End Stage Renal Disease
Conditions
Keywords
etanercept, malnutrition, inflammation, hemodialysis
Brief summary
Etanercept is a novel anti-inflammatory agent currently used in patients with rheumatoid arthritis. We are examining whether Etanercept is effective in improving the nutritional status of hemodialysis patients as a consequence of its ability to decrease inflammation.
Detailed description
Hemodialysis patients with end stage renal disease have a high mortality rate. In individual patients, mortality is associated with a low serum albumin concentration, a marker of poor nutritional status, and with elevated C-reactive protein, a marker of inflammation. Since efforts to improve nutrition through dietary intake have not been successful, inflammation is thought to play a key role in determining nutritional status. Recently, it has been shown that malnutrition, inflammation, and atherosclerosis are closely related in patients with chronic renal failure. It is our hypothesis that suppression of the cycle of inflammation, malnutrition, and vascular injury caused by atherosclerosis will improve survival in dialysis patients. This study is designed to examine whether suppression of the inflammatory response can be accomplished safely with Etanercept and to determine if this suppression will improve nutritional status and clinical outcome in hemodialysis patients with poor nutritional status and evidence of inflammation.
Interventions
DRUGEtanercept
Hemodialysis patients will receive Etanercept at a dose of 25 mg by subcutaneous injection twice a week
DRUGPlacebo
Hemodialysis patients will receive Saline by subcutaneous injection twice a week
Sponsors
Amgen
Dialysis Clinic, Inc.
Kaysen, George A., M.D., Ph.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double Blind Study
Intervention model description
This is a double blind study- one group received 25mg Etanercept twice per week; the other is control - receiving saline twice per week
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Presence of end stage renal disease
Exclusion criteria
* History of Tuberculosis History of Recurrent Infection Recent AMI, Cancer within previous 5 years Presence of Hepatitis B, Hepatitis C, HIV, systemic lupus erythematosis, presence of transcutaneous access (external catheter)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Albumin | 52 weeks | An increased serum albumin (ALB) concentration expected. Higher concentrations of Albumin indicate better outcome. Normal ranges of Albumin in this study is from 3.5 to 5.5 gram per deciliter (g/dL). We expect ALB to remain or increase in this study. |
| C-reactive Protein | 52 weeks | A reduced C-reactive protein (CRP) concentration is expected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prealbumin (mg/dL) | 52 weeks | Effect of treatment on prealbumin (PAB) concentration |
Countries
United States
Participant flow
Recruitment details
The protocol was approved by the Human Subjects Review Committee of the University of California Davis Medical Center and Dialysis Clinics, Incorporated. Screening started in January 2005, and had to be terminated early due to low enrollment in December 2006
Pre-assignment details
Subject was consented and screened for safety. Then they have to qualify for 3 monthly screening values. Once deemed qualified for the study, subject then randomized into a double-blind study; to follow regimen of protocols and followed to 52 weeks of study.
Participants by arm
| Arm | Count |
|---|---|
| Etanercept Etanercept 25 mg injection twice a week
Etanercept: Hemodialysis patients will receive Etanercept at a dose of 25 mg by subcutaneous injection twice a week | 5 |
| Placebo Saline injection twice a week
Placebo: Hemodialysis patients will receive Saline by subcutaneous injection twice a week | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | on-hold due to fistula maturation time | 1 | 0 |
| Overall Study | positive ANA (antinuclear antibody) | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Etanercept | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 7 Participants |
| Age, Continuous | 51 years STANDARD_DEVIATION 16.739 | 55 years STANDARD_DEVIATION 15.209 | 53 years STANDARD_DEVIATION 15.101 |
| Albumin | 3.39 g/dL STANDARD_DEVIATION 0.24 | 3.31 g/dL STANDARD_DEVIATION 0.21 | 3.37 g/dL STANDARD_DEVIATION 0.2 |
| C-Reactive Protein (CRP) | 29.05 mg/L STANDARD_DEVIATION 15.6 | 10.98 mg/L STANDARD_DEVIATION 3.95 | 15.79 mg/L STANDARD_DEVIATION 28.13 |
| Region of Enrollment United States | 5 Participant | 5 Participant | 10 Participant |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 1 / 5 | 1 / 5 |
| serious Total, serious adverse events | 0 / 5 | 3 / 5 |
Outcome results
Primary
Albumin
An increased serum albumin (ALB) concentration expected. Higher concentrations of Albumin indicate better outcome. Normal ranges of Albumin in this study is from 3.5 to 5.5 gram per deciliter (g/dL). We expect ALB to remain or increase in this study.
Time frame: 52 weeks
Population: Hemodialysis patients have a high mortality rate caused by poor nutrition and inflammation. The hypothesis is that suppression of inflammation reverses the malnutrition-inflammation syndrome in hemodialysis patients. Etanercept is an anti-inflammatory agent. Thus it is expected that participant given Etanercept will have a reduced amount of inflammation in their bodies and have better nutritional status - indicated by an increase/steady Albumin level.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept | Albumin | 3.34 g/dL | Standard Deviation 0.22 |
| Placebo | Albumin | 3.42 g/dL | Standard Deviation 0.25 |
Primary
C-reactive Protein
A reduced C-reactive protein (CRP) concentration is expected.
Time frame: 52 weeks
Population: Malnutrition, inflammation, and atherosclerosis affect patients with chronic renal failure. High C-reactive protein is a marker of inflammation. This study is designed to examine whether suppression of the inflammatory response can be accomplished safely with Etanercept. For those who has high CRP level, we expect that CRP level will be reduced
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept | C-reactive Protein | 28.96 mg/L | Standard Deviation 26 |
| Placebo | C-reactive Protein | 11.94 mg/L | Standard Deviation 13.53 |
Secondary
Prealbumin (mg/dL)
Effect of treatment on prealbumin (PAB) concentration
Time frame: 52 weeks
Population: Serum Prealbumin is measured in milligram per deciliter (mg/dL). Increase number is a measured of better nutritional status.~In the etanercept group we would expect fewer decreases in prealbumin. Decreased level of prealbumin may indicate inflammations may be occurring in the body.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept | Prealbumin (mg/dL) | 32.36 mg/dL | Standard Deviation 8.64 |
| Placebo | Prealbumin (mg/dL) | 31.43 mg/dL | Standard Deviation 8.83 |