Niacin to Improve Blood Flow in People With Sickle Cell Disease

NCT00508989 | Completed Phase 2

• 2 other identifiers: 07019607-H-0196
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Sickle Cell Disease

Keywords

Acetylcholine; Forearm Blood Flow; HDL; L-NMMA; Sickle Cell Anemia; Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• The Effect of niacin-ER on endothelial dysfunction in the sickle cell.

  12 weeks

Secondary Outcomes (1)

• Effect of niacin therapy on HDL and apo A-I levels in subjects with sickle cell disease.

  12 weeks

Study Arms (2)

1

EXPERIMENTAL

Drug: Niacin-ER; Drug: L-NMMA; Drug: Acetylcholine

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Niacin-ER DRUG

500 mg daily for 4 weeks, 1000 mg daily for 4 weeks, and 1500 mg daily for 4 weeks

1

Placebo DRUG

500 mg daily for 4 weeks, 1000 mg daily for 4 weeks, and 1500 mg daily for 4 weeks

2

L-NMMA DRUG

1

Acetylcholine DRUG

1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females 18 to 65 years of age.
• Diagnosis of sickle cell disease (electrophoretic or HPLC documentation of hemoglobin S only phenotype is required).
• Hemoglobin greater than 5.5 grams per deciliter
• Absolute reticulocyte count greater than 95,000 microliters if hemoglobin is less than 9.0 grams per deciliter.
• An apoA-1 level lower than 99 milligrams per deciliter (median value among sickle cell subjects), or HDL-C level below 39 milligrams per deciliter (median value amongst our sickle cell cohort).

You may not qualify if:

• Acute pain crisis requiring intravenous analgesics within the last week.
• Current pregnancy or lactation.
• Hemoglobin SC disease, or hemoglobin A greater than 20%
• Conditions that may independently affect endothelial function:
• Diabetes mellitus
• Cigarette smoking within one month
• Uncontrolled hypertension
• Serum creatinine greater than 2.0 milligram per deciliter
• Uric acid level greater than 8 or history of gout
• History of GI bleeding within the past 6 months
• Active peptic ulcer disease
• Hemoglobin less than or equal to 5.5 grams per deciliter; however, subjects may return for evaluation at a later date.
• No aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) for 1 week prior to forearm blood flow assessment and no caffeine the day of each forearm blood flow study. Subjects on opiates or acetaminophen will not be excluded.
• Subjects taking sildenafil, vardenafil, tadalafil, L-arginine, fibrates (e.g., clofibrate, gemfibrozil, or fenofribrate) or inhaled nitric oxide within the last week will be excluded from the study.
• Subjects taking any statin drug (e.g., fluvastatin, lovastatin, pravastatin, simvastatin, rosuvastatin) within the last four weeks will be excluded from the study.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (2)

Howard University Hospital

Washington D.C., District of Columbia, 20060, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Barter PJ, Nicholls S, Rye KA, Anantharamaiah GM, Navab M, Fogelman AM. Antiinflammatory properties of HDL. Circ Res. 2004 Oct 15;95(8):764-72. doi: 10.1161/01.RES.0000146094.59640.13.

  PMID: 15486323 BACKGROUND

• Kwiterovich PO Jr. The antiatherogenic role of high-density lipoprotein cholesterol. Am J Cardiol. 1998 Nov 5;82(9A):13Q-21Q. doi: 10.1016/s0002-9149(98)00808-x.

  PMID: 9819099 BACKGROUND

• Viswambharan H, Ming XF, Zhu S, Hubsch A, Lerch P, Vergeres G, Rusconi S, Yang Z. Reconstituted high-density lipoprotein inhibits thrombin-induced endothelial tissue factor expression through inhibition of RhoA and stimulation of phosphatidylinositol 3-kinase but not Akt/endothelial nitric oxide synthase. Circ Res. 2004 Apr 16;94(7):918-25. doi: 10.1161/01.RES.0000124302.20396.B7. Epub 2004 Feb 26.

  PMID: 14988229 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

omega-N-Methylarginine; Acetylcholine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Biogenic Amines; Amines; Organic Chemicals

Study Officials

• John F Tisdale, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2007
• First Posted: July 30, 2007
• Study Start: July 24, 2007
• Primary Completion: December 31, 2010
• Study Completion: December 24, 2015
• Last Updated: September 10, 2020

Record last verified: 2015-12-24

Locations

US (2)