Atherosclerosis, Cardiovascular Disease, Dialysis, Inflammation
Conditions
Brief summary
Patients with kidney failure on hemodialysis have an extremely high rate of cardiovascular disease including atherosclerotic cardiovascular disease. This, at least in part, is due to the chronic inflammatory status usually seen in these patients. Here we try to see if treatment with extended release nicotinic acid (Niaspan) can reduce their overall inflammatory burden (in general) and the atherosclerotic plaque inflammation (in particular).
Interventions
DRUGExtended Release Nicotinic Acid (Niaspan)
Subjects will start on 500 mg per day of Niaspan for 4 weeks, then the dose will be increased to 1000 mg per day of Niaspan for 4 weeks, then the dose will be increased to 1500 mg of Niaspan per day for 4 weeks, after this subjects with weight of less than 60 kg will continue at 1500 mg per day of Niaspan for another 12 weeks whereas in subjects with weight of more than 60 kg the dose will be increased to 2000 mg of Niaspan per day which will be continued for 12 weeks.
Sponsors
Brigham and Women's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A signed consent form; * Male or Female, 18 years or older; * Diagnosed with ESRD, on maintenance hemodialysis for at least six (6) months; * Subject must be able to understand and provide informed consent; * No known contraindications to therapy with nicotinic acid; * Female subjects of childbearing potential must be willing to be on an acceptable form of birth control for the duration of the study and for two month after they have stopped taking the study drug.
Exclusion criteria
* Any patient with a medical condition or taking any medications that would be contraindicated with the use of extended release niacin, such as active peptic ulcer disease; * History of severe allergic reactions to the study medication; * History of active infection or acute gouty attack within 2 weeks prior to enrollment; * Known serological positivity for HIV, HBsAg, or HCV Ab; * HbA1C \> 9; * Total CK of more than three times of the upper limit of normal; * Elevation of liver function tests at time of entry (AST and/or ALT \> 2 times the upper limit of normal); * History of drug, alcohol, or chemical abuse within 6 months prior to enrollment; * History of malignancy except adequately treated in-situ cervical carcinoma, or adequately treated basal or squamous cell carcinoma of the skin; * History of an inflammatory disease such as SLE, rheumatoid arthritis or ulcerative colitis; * Patients currently on pharmacological doses of nicotinic acid; * Patients receiving chronic anti-inflammatory therapy; * Patients with average baseline hs-CRP levels of \> 20 mg/L or \< 1 mg/L; * Patients in whom FDG-PET/CT dual scans are contraindicated (e.g., pregnant patients or those with severe allergy to IV contrast; a pregnancy test will be performed in each female subject between 18 and 45 years of age prior to each scan)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in FDG-PET/CT Dual Scan Score | 6 months | — |
| Changes in Hs-CRP Level | 6 months | Change in hs-CRP level before and after treatment in each subject |
| Changes in IL-6 Level | 6 months | Change in IL-6 level before and after treatment in each subject |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Cardiovascular Events | 6 months | Comparison of the average major cardiovascular events (myocardial infarction and/or stroke) in the 3 month before and the last 3 months of the study. |
| Albumin Level | 6 months | Pre and Post levels. |
| Number of Completed Subjects With Significant Increase in ALT (Alanine Aminotransferase). | 6 months (checked monthly) | The number of subjects with significant rise in ALT but not to the extent requiring removal from the study (rise to more than 3 times the upper limit of the normal range) |
| Hemodialysis Access Stenosis/Thrombosis | 6 months | Comparison of the average hemodialysis access stenosis/thrombosis requiring intervention in the 3 month before and the last 3 months of the study. |
| ESA (Erythorpoietic Stimulating Agent) Dose Requirement | 6 months | Comparison of the average ESA dose used in the 3 month before and the last 3 months of the study. |
| Hemoglobin Level | 6 months | Pre and Post Levels |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group (One Arm Only Study) Blood sample and scan results to be compared before and after intervention in each subject.
Extended Release Nicotinic Acid (Niaspan): Subjects will start on 500 mg per day of Niaspan for 4 weeks, then the dose will be increased to 1000 mg per day of Niaspan for 4 weeks, then the dose will be increased to 1500 mg of Niaspan per day for 4 weeks, after this subjects with weight of less than 60 kg will continue at 1500 mg per day of Niaspan for another 12 weeks whereas in subjects with weight of more than 60 kg the dose will be increased to 2000 mg of Niaspan per day which will be continued for 12 weeks. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Treatment Group (One Arm Only Study) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 58.9 years |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 22 |
| serious Total, serious adverse events | 1 / 22 |
Outcome results
Primary
Changes in FDG-PET/CT Dual Scan Score
Time frame: 6 months
Population: Analysis of images for this outcome measure was not done given than only 2 subjects had completed the study at the time of the study early termination and closure (per funding source)
| Arm | Measure | Value |
|---|---|---|
| Treatment Group (One Arm Only Study) | Changes in FDG-PET/CT Dual Scan Score | 0 |
Primary
Changes in Hs-CRP Level
Change in hs-CRP level before and after treatment in each subject
Time frame: 6 months
Population: Only 2 subjects completed the study. Power for further analysis was not met.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Group (One Arm Only Study) | Changes in Hs-CRP Level | Average Pre-Treatment | 18.465 mg/L |
| Treatment Group (One Arm Only Study) | Changes in Hs-CRP Level | Average Post-Treatment | 26.395 mg/L |
Primary
Changes in IL-6 Level
Change in IL-6 level before and after treatment in each subject
Time frame: 6 months
Population: Only 2 subjects completed the study. Further analysis not done because power was not met.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Group (One Arm Only Study) | Changes in IL-6 Level | Average Pre-Treatment | 5.1254 pg/mL |
| Treatment Group (One Arm Only Study) | Changes in IL-6 Level | Average Post-Treatment | 14.8375 pg/mL |
Secondary
Albumin Level
Pre and Post levels.
Time frame: 6 months
Population: Only 2 subjects completed the study. Further analysis was not done because power was not met.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Group (One Arm Only Study) | Albumin Level | Average Pre-Treatment | 3.9 g/dL |
| Treatment Group (One Arm Only Study) | Albumin Level | Average Post-Treatment | 4.05 g/dL |
Secondary
ESA (Erythorpoietic Stimulating Agent) Dose Requirement
Comparison of the average ESA dose used in the 3 month before and the last 3 months of the study.
Time frame: 6 months
Population: Data for this outcome measure was not collected.
| Arm | Measure | Value |
|---|---|---|
| Treatment Group (One Arm Only Study) | ESA (Erythorpoietic Stimulating Agent) Dose Requirement | 0 |
Secondary
Hemodialysis Access Stenosis/Thrombosis
Comparison of the average hemodialysis access stenosis/thrombosis requiring intervention in the 3 month before and the last 3 months of the study.
Time frame: 6 months
Population: Data for this outcome measure was not collected from the medical record due to early termination of the study.
| Arm | Measure | Value |
|---|---|---|
| Treatment Group (One Arm Only Study) | Hemodialysis Access Stenosis/Thrombosis | 0 |
Secondary
Hemoglobin Level
Pre and Post Levels
Time frame: 6 months
Population: Only 2 subjects completed the study. Further analysis was not done because power was not met.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment Group (One Arm Only Study) | Hemoglobin Level | Average Pre-Treatment | 11.6 g/dL |
| Treatment Group (One Arm Only Study) | Hemoglobin Level | Average Post-Treatment | 10.15 g/dL |
Secondary
Number of Completed Subjects With Significant Increase in ALT (Alanine Aminotransferase).
The number of subjects with significant rise in ALT but not to the extent requiring removal from the study (rise to more than 3 times the upper limit of the normal range)
Time frame: 6 months (checked monthly)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group (One Arm Only Study) | Number of Completed Subjects With Significant Increase in ALT (Alanine Aminotransferase). | 0 Participants |
Secondary
Rate of Cardiovascular Events
Comparison of the average major cardiovascular events (myocardial infarction and/or stroke) in the 3 month before and the last 3 months of the study.
Time frame: 6 months
Population: Data for this outcome measure was not collected from the medical record due to early termination of the study.
| Arm | Measure | Value |
|---|---|---|
| Treatment Group (One Arm Only Study) | Rate of Cardiovascular Events | 0 |