Niacin to Improve Blood Flow in People With Sickle Cell Disease

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

Interventions

DRUG

Niacin-ER

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

DRUG

Placebo

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

DRUG

L-NMMA

DRUG

Acetylcholine

Sponsors & Collaborators

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

  lead NIH

Principal Investigators

• John F Tisdale, M.D. · National Heart, Lung, and Blood Institute (NHLBI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-07-24

Primary Completion

2010-12-31

Completion

2015-12-24

Countries

• United States

Study Locations