Ignite Creation Date:
2024-05-05 @ 6:34 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00508989
Status:
COMPLETED
Last Update Posted:
2020-09-10
First Post:
2007-07-27
Brief Title:
Niacin to Improve Blood Flow in People With Sickle Cell Disease
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Niacin Therapy to Improve Endothelial Function in Sickle Cell Disease
Status:
COMPLETED
Status Verified Date:
2015-12-24
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will determine whether niacin can improve blood flow in people with sickle cell disease in which abnormal red blood cells interfere with blood flow to cause the disease symptoms Niacin a drug that has been used to increase HDL good cholesterol levels improves blood flow in people without sickle cell disease This study will see if it can do the same in people with the disease
Patients with sickle cell disease between 18 and 65 years of age may be eligible for this study
Candidates are screened with a medical history physical examination blood tests echocardiogram and 6-minute walk test of exercise capacity
Participants have the following baseline blood flow studies
Flow-mediated dilation FMD An ultrasound picture of the artery in the forearm is obtained A blood pressure cuff is then placed on the upper arm and inflated for 5 minutes After the pressure cuff is released the ultrasound is repeated
Peripheral artery tonometry PAT A sensor is placed on the subject s finger The sensor puts pressure on the finger and measures blood flow
Standard forearm blood flow test Small tubes are placed in the artery of the forearm at the inside of the elbow Saline is infused into one tube Pressure cuffs are applied to the wrist and upper arm A strain gauge rubber band device is placed around the forearm When the cuffs are inflated blood flows into the arm stretching the strain gauge and the flow measurement is recorded Blood samples are collected from the tube in the artery to measure blood counts proteins and other chemicals At various times small doses of the following drugs are administered through the tube in the vein
Sodium nitroprusside causes blood vessels to dilate and increases blood flow to the heart
Acetylcholine causes blood vessels to dilate and slows heart rate
LNMMA decreases blood flow by blocking the production of nitric oxide
Blood flow is measured after each dose of the different drugs There are rest periods between injections of the different drugs Pictures of the forearm are taken during the studies using an infrared camera and computer
-Drug Treatment Participants are assigned to take three 4-week courses of niacin or placebo They return to the Clinical Center at the following intervals from the time they start the test drug for followup
Weeks 2 6 and 10 Brief medical history review of medication side effects and blood tests
Weeks 4 and 8 Physical examination brief medical history review of medication side effects and blood tests repeat FMD and PAT blood flow studies and 6-minute walk test
Week 12 Same as weeks 4 and 8 plus standard blood flow studies and echocardiogram
Patients with sickle cell disease between 18 and 65 years of age may be eligible for this study
Candidates are screened with a medical history physical examination blood tests echocardiogram and 6-minute walk test of exercise capacity
Participants have the following baseline blood flow studies
Flow-mediated dilation FMD An ultrasound picture of the artery in the forearm is obtained A blood pressure cuff is then placed on the upper arm and inflated for 5 minutes After the pressure cuff is released the ultrasound is repeated
Peripheral artery tonometry PAT A sensor is placed on the subject s finger The sensor puts pressure on the finger and measures blood flow
Standard forearm blood flow test Small tubes are placed in the artery of the forearm at the inside of the elbow Saline is infused into one tube Pressure cuffs are applied to the wrist and upper arm A strain gauge rubber band device is placed around the forearm When the cuffs are inflated blood flows into the arm stretching the strain gauge and the flow measurement is recorded Blood samples are collected from the tube in the artery to measure blood counts proteins and other chemicals At various times small doses of the following drugs are administered through the tube in the vein
Sodium nitroprusside causes blood vessels to dilate and increases blood flow to the heart
Acetylcholine causes blood vessels to dilate and slows heart rate
LNMMA decreases blood flow by blocking the production of nitric oxide
Blood flow is measured after each dose of the different drugs There are rest periods between injections of the different drugs Pictures of the forearm are taken during the studies using an infrared camera and computer
-Drug Treatment Participants are assigned to take three 4-week courses of niacin or placebo They return to the Clinical Center at the following intervals from the time they start the test drug for followup
Weeks 2 6 and 10 Brief medical history review of medication side effects and blood tests
Weeks 4 and 8 Physical examination brief medical history review of medication side effects and blood tests repeat FMD and PAT blood flow studies and 6-minute walk test
Week 12 Same as weeks 4 and 8 plus standard blood flow studies and echocardiogram
Detailed Description:
Sickle cell disease is an autosomal recessive disorder and the most common genetic disease affecting African-Americans Approximately 015 percent of African-Americans are homozygous for sickle cell disease and 8 percent have sickle cell trait Hemoglobin S polymerization leads to red cell rigidity microvascular obstruction inflammation and end-organ ischemic injury Our published data indicate that up to 50 percent of sickle cell patients have vascular dysfunction due to impaired bioavailability of endogenous nitric oxide due in large part to scavenging of nitric oxide by cell-free hemoglobin We recently have completed studies that directly demonstrate endothelial dysfunction in patients with sickle cell disease characterized by decreased ACh dependent vasorelaxation in forearm blood flow studies distinct from the nitric oxide resistance above Further we have found in sickle cell patients a new association between low levels of apoA-I pulmonary hypertension and endothelial dysfunction Raising levels of HDL and therefore apoA-1 could have the effect of ameliorating the endothelial dysfunction characteristic of sickle cell disease by affecting endothelium dependent vasorelaxation Therapies directed at restoring HDL in these patients may be beneficial
HDL is thought to promote vascular health in a variety of ways some of which are unrelated to lipid transport One of the best-known mechanisms relates to efflux of cholesterol from atherosclerotic plaque yet HDL is thought to have several antithrombotic and anti-inflammatory effects In vitro HDL attenuates formation of oxidized LDL and inhibits endothelial cell expression of inflammatory cell adhesion molecules It is also thought to mediate NO production via stimulation of eNOS thereby modulating endothelial function In a study of subjects with atherosclerosis low HDL levels correlated with impaired vasomotor relaxation via brachial artery FMD Another study utilizing recombinant HDL cholesterol infused into brachial arteries of hypercholesterolemic men resulted in increased acetylcholine mediated blood flow that was inhibited by the infusion of L-NAME an eNOS inhibitor suggesting that HDL increased blood flow via an eNOS dependent mechanism This may have implications not only for subjects with atherosclerosis but also for those with sickle cell disease and endothelial dysfunction
We propose that niacin therapy could improve vascular reactivity in response to acetylcholine Several options for increasing HDL levels have been previously utilized in forearm flow studies using venous occlusion plethysmography or flow-mediated dilation Reconstituted HDL rHDL apoA-1 mimetics and niacin therapy were all shown to improve endothelial dysfunction and proved safe and effective
This trial will aim to 1 establish the effects of niacin treatment on raising HDL levels in subjects with sickle cell disease 2 investigate whether niacin treatment would result in improvement of endothelial-dependent relaxation via venous occlusion plethysmography and 3 compare the efficacy of peripheral arterial tonometry measurements to venous occlusion plethysmography and flow-mediated dilation as indicators of vascular dysfunction
HDL is thought to promote vascular health in a variety of ways some of which are unrelated to lipid transport One of the best-known mechanisms relates to efflux of cholesterol from atherosclerotic plaque yet HDL is thought to have several antithrombotic and anti-inflammatory effects In vitro HDL attenuates formation of oxidized LDL and inhibits endothelial cell expression of inflammatory cell adhesion molecules It is also thought to mediate NO production via stimulation of eNOS thereby modulating endothelial function In a study of subjects with atherosclerosis low HDL levels correlated with impaired vasomotor relaxation via brachial artery FMD Another study utilizing recombinant HDL cholesterol infused into brachial arteries of hypercholesterolemic men resulted in increased acetylcholine mediated blood flow that was inhibited by the infusion of L-NAME an eNOS inhibitor suggesting that HDL increased blood flow via an eNOS dependent mechanism This may have implications not only for subjects with atherosclerosis but also for those with sickle cell disease and endothelial dysfunction
We propose that niacin therapy could improve vascular reactivity in response to acetylcholine Several options for increasing HDL levels have been previously utilized in forearm flow studies using venous occlusion plethysmography or flow-mediated dilation Reconstituted HDL rHDL apoA-1 mimetics and niacin therapy were all shown to improve endothelial dysfunction and proved safe and effective
This trial will aim to 1 establish the effects of niacin treatment on raising HDL levels in subjects with sickle cell disease 2 investigate whether niacin treatment would result in improvement of endothelial-dependent relaxation via venous occlusion plethysmography and 3 compare the efficacy of peripheral arterial tonometry measurements to venous occlusion plethysmography and flow-mediated dilation as indicators of vascular dysfunction
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 07-H-0196 | None | None | None |