Hypoalbuminemia
Conditions
Keywords
Inflammation, albumin
Brief summary
Both malnutrition and inflammation are associated with death in dialysis patients and also with cardiovascular disease. The researchers are testing the idea that inflammation causes malnutrition by using a drug to suppress inflammation in hemodialysis patients to find out whether that will increase blood tests that are associated with malnutrition. The researchers will give hemodialysis patients who have both inflammation and malnutrition either thalidomide or a placebo and compare the effects of treatment on the levels of two proteins in the blood, albumin and prealbumin, that are normally reduced in malnourished patients. Patients who have a serum albumin concentration \< 3.8 g/dl will be asked to sign consent to have blood drawn prior to dialysis for measurement of CRP (C-reactive protein). Those with CRP values ≥ 0.8 mg/dl will have a second measurement of CRP performed within 2 weeks. Those with two consecutive values of CRP ≥ 0.8 mg/dl will be eligible for enrollment
Detailed description
4.1 Pre-assignment measurements will include: 1. Patient is eligible for enrollment. 2. Complete physical examination. 3. Blood draw at initiation of hemodialysis session 4. Instruction on birth control methods required. 5. Subjects who are non-compliant with regard to medication compliance range or birth control requirements as outlined in the S.T.E.P.S.® program will be immediately discontinued from the study 4.2 Detailed description of treatment: Patients who completed the first 4 weeks will be randomized into Treatment group. A total of 24 subjects will be studied; 12 will receive no drug and 12 will receive thalidomide. Subjects randomized to Active Treatment arm will receive Placebo (no-drug/sugar pill) ,or thalidomide 100 mg (two 50 mg active capsules) to take at bedtime. Weekly, Subjects will have blood drawn; will undergo a capsule count to establish a compliance range of \> 85%; will have physical exam with special attention to skin and evaluation of peripheral nervous system for a change in or appearance of sensory neuropathy. If somnolence is tolerable (subjects do not have residual somnolence in the morning) the dose will be increased to 200 mg (4 capsules). Patients who completed 24 weeks of study will have final evaluation at week 28.
Interventions
OTHERSugar pill
Placebo by mouth at night for a total of 24 weeks
DRUGThalidomide
Thalidomide by mouth at night for a total of 24 weeks
Sponsors
Beth Israel Medical Center
George A. Kaysen, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. End stage renal disease (ESRD) patients on hemodialysis for at least 3 months. 2. Serum C reactive protein level of ≥ 0.8 mg/dl. 3. Serum albumin \< 3.8 g/dl (BCG). 4. Signing a written informed consent form. 5. Willingness and ability to comply with the FDA-mandated S.T.E.P.S ® program. 6. Age \> 18 years.
Exclusion criteria
1. Pregnant and/ or lactating female. 2. Active infection within the previous 8 weeks requiring administration of antibiotics. 3. Patients receiving systemic immunosuppressive therapy. 4. Patients with HIV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Serum Albumin | 28 weeks total | Serum albumin in treated patient and control (no drug) patients were tabulated once weekly for week #1-4 , then once every 4 weeks thereafter at week# 8, 12, 16, 20, 24 to see changes of health status. Final data collected at week 28 -- to ensure patient safety |
| Difference in Serum CRP | 28 weeks total | Serum CRP in treated patient and control (no drug) patients were tabulated once weekly for week #1-4 , then once every 4 weeks thereafter at week# 8, 12, 16, 20, 24 to see changes of health status. Final data collected at week 28 -- to ensure patient safety |
| Difference in Serum Prealbumin | 28 weeks total | Serum Prealbumin in treated patient and control (no drug) patients were tabulated once weekly for week #1-4 , then once every 4 weeks thereafter at week# 8, 12, 16, 20, 24 to see changes of health status. Final data collected at week 28 -- to ensure patient safety |
Countries
United States
Participant flow
Recruitment details
The study has been terminated due to lack of participation. We enrolled 16 subjects according to eligibility. 4 subjects randomized into the study. Two subjects completed the study.
Pre-assignment details
Subject enrollment into the active study must meet capsule count of \>85% compliance with regard to medication and/or birth control requirements as outlined in the S.T.E.P.S ® in the first 4 weeks of study program
Participants by arm
| Arm | Count |
|---|---|
| Thalidomide 1. 12 End stage renal disease (ESRD) patients on hemodialysis for at least 3 months
2. Serum C reactive protein level of ≥ 0.8 mg/dl
3. Serum albumin \< 3.8 g/dl (BCG)
4. Patients will receive Thalidomide for a period of 24 weeks.100 mg by mouth at night for 4 weeks; then if tolerated, Thalidomid will be increased to 200 mg by mouth at night for 20 weeks; for a total of 24 weeks on Thalidomid | 2 |
| Placebo 1. 12 End stage renal disease (ESRD) patients on hemodialysis for at least 3 months
2. Serum C reactive protein level of ≥ 0.8 mg/dl
3. Serum albumin \< 3.8 g/dl (BCG)
4. Patients will receive Placebo for a period of 24 weeks. | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Thalidomide | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 2 | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
Difference in Serum Albumin
Serum albumin in treated patient and control (no drug) patients were tabulated once weekly for week #1-4 , then once every 4 weeks thereafter at week# 8, 12, 16, 20, 24 to see changes of health status. Final data collected at week 28 -- to ensure patient safety
Time frame: 28 weeks total
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thalidomide | Difference in Serum Albumin | week 8 | 3.8 g/dL of Albumin |
| Thalidomide | Difference in Serum Albumin | week 1 | 3.4 g/dL of Albumin |
| Thalidomide | Difference in Serum Albumin | week 3 | 3.5 g/dL of Albumin |
| Thalidomide | Difference in Serum Albumin | week 16 | 3.5 g/dL of Albumin |
| Thalidomide | Difference in Serum Albumin | week 20 | 2.9 g/dL of Albumin |
| Thalidomide | Difference in Serum Albumin | week 12 | 3.6 g/dL of Albumin |
| Thalidomide | Difference in Serum Albumin | week 24 | 3.6 g/dL of Albumin |
| Thalidomide | Difference in Serum Albumin | week 4 | 3.6 g/dL of Albumin |
| Thalidomide | Difference in Serum Albumin | week 28 | 3.5 g/dL of Albumin |
| Thalidomide | Difference in Serum Albumin | week 2 | 3.7 g/dL of Albumin |
| Placebo | Difference in Serum Albumin | week 28 | 3.9 g/dL of Albumin |
| Placebo | Difference in Serum Albumin | week 1 | 3.7 g/dL of Albumin |
| Placebo | Difference in Serum Albumin | week 2 | 3.5 g/dL of Albumin |
| Placebo | Difference in Serum Albumin | week 3 | 3.4 g/dL of Albumin |
| Placebo | Difference in Serum Albumin | week 4 | 4.0 g/dL of Albumin |
| Placebo | Difference in Serum Albumin | week 8 | 3.6 g/dL of Albumin |
| Placebo | Difference in Serum Albumin | week 12 | 4.1 g/dL of Albumin |
| Placebo | Difference in Serum Albumin | week 20 | 3.8 g/dL of Albumin |
| Placebo | Difference in Serum Albumin | week 24 | 3.9 g/dL of Albumin |
| Placebo | Difference in Serum Albumin | week 16 | 4.0 g/dL of Albumin |
Primary
Difference in Serum CRP
Serum CRP in treated patient and control (no drug) patients were tabulated once weekly for week #1-4 , then once every 4 weeks thereafter at week# 8, 12, 16, 20, 24 to see changes of health status. Final data collected at week 28 -- to ensure patient safety
Time frame: 28 weeks total
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thalidomide | Difference in Serum CRP | week 16 | NA Mg/L CRP |
| Thalidomide | Difference in Serum CRP | week 1 | NA Mg/L CRP |
| Thalidomide | Difference in Serum CRP | week 2 | NA Mg/L CRP |
| Thalidomide | Difference in Serum CRP | week 3 | NA Mg/L CRP |
| Thalidomide | Difference in Serum CRP | week 4 | NA Mg/L CRP |
| Thalidomide | Difference in Serum CRP | week 8 | NA Mg/L CRP |
| Thalidomide | Difference in Serum CRP | week 12 | NA Mg/L CRP |
| Thalidomide | Difference in Serum CRP | week 20 | NA Mg/L CRP |
| Thalidomide | Difference in Serum CRP | week 24 | NA Mg/L CRP |
| Thalidomide | Difference in Serum CRP | week 28 | NA Mg/L CRP |
| Placebo | Difference in Serum CRP | week 20 | 1.92 Mg/L CRP |
| Placebo | Difference in Serum CRP | week 16 | 3.41 Mg/L CRP |
| Placebo | Difference in Serum CRP | week 8 | 2.87 Mg/L CRP |
| Placebo | Difference in Serum CRP | week 1 | 1.76 Mg/L CRP |
| Placebo | Difference in Serum CRP | week 28 | 3.93 Mg/L CRP |
| Placebo | Difference in Serum CRP | week 2 | 2.07 Mg/L CRP |
| Placebo | Difference in Serum CRP | week 12 | 2.87 Mg/L CRP |
| Placebo | Difference in Serum CRP | week 3 | 1.76 Mg/L CRP |
| Placebo | Difference in Serum CRP | week 24 | 6.01 Mg/L CRP |
| Placebo | Difference in Serum CRP | week 4 | 2.29 Mg/L CRP |
Primary
Difference in Serum Prealbumin
Serum Prealbumin in treated patient and control (no drug) patients were tabulated once weekly for week #1-4 , then once every 4 weeks thereafter at week# 8, 12, 16, 20, 24 to see changes of health status. Final data collected at week 28 -- to ensure patient safety
Time frame: 28 weeks total
Population: Participant data is not available due to no shipping of specimen to analyzing laboratory