Novel Pathways to Manage Inflammation and Atherosclerosis in Dialysis Patients: Role of Nicotinic Acid

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01159054
• Collaborator: (none)
• Enrollment: 22
• Locations: 3
• Arm: 1
• Duration (Months): 53
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Dialysis; Cardiovascular Disease; Atherosclerosis; Inflammation	Drug: Extended Release Nicotinic Acid (Niaspan)	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Novel Pathways to Manage Inflammation and Atherosclerosis in Dialysis Patients: Role of Nicotinic Acid
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: This study has only one arm. Blood sample and scan results to be compared before and after intervention in each subject.

Drug: 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.; Other Names: Extended Release Nicotinic Acid Niaspan

Outcome Measures

Primary Outcome Measures

1. Changes in FDG-PET/CT Dual Scan Score [6 months]

2. Changes in Hs-CRP Level [6 months]

   Change in hs-CRP level before and after treatment in each subject

3. Changes in IL-6 Level [6 months]

   Change in IL-6 level before and after treatment in each subject

Secondary Outcome Measures

1. Albumin Level [6 months]

   Pre and Post levels.

2. 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.

3. Hemoglobin Level [6 months]

   Pre and Post Levels

4. 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.

5. 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.

6. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
2	BWH/FH/DCI Outpatient Dialysis Unit	Boston	Massachusetts	United States	02130
3	DCI Dialysis Unit-Somerville	Somerville	Massachusetts	United States

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

• Principal Investigator: Kambiz ZANDI-NEJAD, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kambiz Zandi-Nejad, MD, Instructor in Medicine, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01159054
• Other Study ID Numbers: 2010P001049
• First Posted: Jul 9, 2010
• Last Update Posted: Jun 28, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Cardiovascular Diseases; Atherosclerosis; Inflammation; Niacin; Nicotinic Acids; Niacinamide

Study Results

Participant Flow

Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	22
COMPLETED	2
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Overall Participants	22
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	14 63.6%
>=65 years	8 36.4%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58.9
Sex: Female, Male (Count of Participants)
Female	11 50%
Male	11 50%
Region of Enrollment (participants) [Number]
United States	22 100%

Outcome Measures

1. Primary Outcome

Title	Changes in FDG-PET/CT Dual Scan Score
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

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/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Measure Participants	0
	0

2. Primary Outcome

Title	Changes in Hs-CRP Level
Description	Change in hs-CRP level before and after treatment in each subject
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Only 2 subjects completed the study. Power for further analysis was not met.

Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Measure Participants	2
Average Pre-Treatment	18.465
Average Post-Treatment	26.395

3. Primary Outcome

Title	Changes in IL-6 Level
Description	Change in IL-6 level before and after treatment in each subject
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Only 2 subjects completed the study. Further analysis not done because power was not met.

Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Measure Participants	2
Average Pre-Treatment	5.1254
Average Post-Treatment	14.8375

4. Secondary Outcome

Title	Albumin Level
Description	Pre and Post levels.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Only 2 subjects completed the study. Further analysis was not done because power was not met.

Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Measure Participants	2
Average Pre-Treatment	3.9
Average Post-Treatment	4.05

5. Secondary Outcome

Title	ESA (Erythorpoietic Stimulating Agent) Dose Requirement
Description	Comparison of the average ESA dose used in the 3 month before and the last 3 months of the study.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected.

Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Measure Participants	0
	0

6. Secondary Outcome

Title	Hemoglobin Level
Description	Pre and Post Levels
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Only 2 subjects completed the study. Further analysis was not done because power was not met.

Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Measure Participants	2
Average Pre-Treatment	11.6
Average Post-Treatment	10.15

7. Secondary Outcome

Title	Rate of Cardiovascular Events
Description	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

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected from the medical record due to early termination of the study.

Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Measure Participants	0
	0

8. Secondary Outcome

Title	Hemodialysis Access Stenosis/Thrombosis
Description	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

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected from the medical record due to early termination of the study.

Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Measure Participants	0
	0

9. Secondary Outcome

Title	Number of Completed Subjects With Significant Increase in ALT (Alanine Aminotransferase).
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
Measure Participants	2
Number [Participants]	0 0%

Adverse Events

Time Frame	6 months (the time between the first and the second scan)
Arm/Group Title	Treatment Group (One Arm Only Study)
Arm/Group Description	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.
All Cause Mortality
	Treatment Group (One Arm Only Study)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment Group (One Arm Only Study)
	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)
Cardiac disorders
Atrial Fibrillation	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	Treatment Group (One Arm Only Study)
	Affected / at Risk (%)	# Events
Total	2/22 (9.1%)
Gastrointestinal disorders
GI upset	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Flushing	2/22 (9.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.