The Role of Cytokines on Growth Hormone Suppression in Premenopausal Women With Rheumatoid Arthritis and the Effect of Treatment With Etanercept

Healthy Clinical Trial

Official title: Suppression of the Growth Hormone/ Insulin-Like Growth Factor-1 (GH/IGF-1) Axis in Women With Rheumatoid Arthritis

Status Completed

Clinical Trial Summary

This study has two phases. Phase 1 will examine the role of inflammatory mediators called cytokines on growth hormone levels in women with rheumatoid arthritis (RA). Phase 2 will evaluate the effect of etanercept on these growth hormone levels. Etanercept is approved for the treatment of RA. It lowers the levels of a key inflammatory mediator called tumor necrosis factor-alpha and is very effective in reducing arthritis symptoms.

Growth hormone promotes bone and muscle growth. With aging, people lose muscle mass and bone strength, possibly because of decreased levels of growth hormone. People with RA have bone and muscle changes similar to those in older people, perhaps also due to decreased levels of growth hormone. The first part of this study will see if the inflammatory mediators responsible for joint inflammation (warmth, redness, pain, and swelling) in RA are related to the lowered growth hormone levels in this disease. The second part will evaluate the effect of etanercept treatment on muscle mass and bone density, in addition to growth hormone levels.

Premenopausal women between 18 and 55 years of age with a recent diagnosis of rheumatoid arthritis (less than 3 years) are eligible for this study. Healthy volunteers will also be enrolled in the first phase of the study as control subjects. This study is conducted at two sites, the NIH and the Johns Hopkins Medical Center in Baltimore.

Healthy volunteers enrolled in this study will be interviewed about their health status and will fill out questionnaires on diet and general physical function, including fatigue, energy and well being. In addition, they will be hospitalized once at the NIH Clinical Center for 24-hour blood sampling and will visit to Johns Hopkins Medical Center in Baltimore for a brachial artery reactivity study, as follows:

• 24-hour blood sampling for growth hormone levels. Blood samples (1/2 teaspoon each) will be collected every 20 minutes from 8 AM one day until 8 AM the following day through a plastic tube in an arm vein.

• Dual energy X-ray absorptiometry (DEXA) scan on a small area of the spine, hip and wrist to assess bone density and a total body DEXA scan to assess the amount and distribution of muscle and body fat.

• Blood vessel (brachial artery reactivity) study to measure the ability of the brachial artery to dilate and increase its blood flow. For this procedure, the subject lies on a table with electrocardiogram leads attached to the chest. A blood pressure cuff is inflated for several minutes and a drop of nasal spray of nitroglycerin is given that may cause a headache. Blood pressure and headache are monitored and treated as needed.

Patients with rheumatoid arthritis will be seen at the NIH clinic on six separate visits (weeks 0, 1, 6, 12, 18, and 26) over 26 weeks. Week 0 is a screening visit. At weeks 1 and 26, patients will be admitted to the hospital for 24-hour blood sampling, DEXA scans, and brachial artery reactivity tests, as described above, plus X-rays of the hand and feet. After the first visit, they will start taking etanercept, given by self-injection under the skin (like insulin shots) twice a week. Follow-up visits at weeks 6, 12, and 18 will involve evaluations of disease activity and drug side effects through joint examination, blood tests, and questionnaires.

Clinical Trial Description

This is a study in pre-menopausal and perimenopausal women with onset of rheumatoid arthritis (RA) of less than 10 years duration, to be conducted at the Clinical Center of National Institutes of Health and The General Clinical Research Center of the Johns Hopkins Bayview Medical Center, Baltimore, MD. This investigation will explore the possible impact of systemically released inflammatory cytokines on suppression of the GH/IGF-1 axis, and the relationships of altered endocrine-immune function with body composition, endocrine, metabolic and vascular functions thought to be associated with RA-related sarcopenia, osteopenia and increased cardiovascular risk. In phase I of the study, we shall admit RA patients and control subjects to the Clinical Center for a 26-36 hour period for assessments of the GH/IGF-I axis, cytokines, body composition, endocrine-metabolic and cardiovascular functions, and quality of life. We plan to initiate Phase I of the study to compare baseline endocrine and inflammatory parameters in RA patients to matched normal controls. Phase II of the study, we shall enroll a new group of RA patients to evaluate the above outcome measures at baseline and after six months of treatment with standard therapy, using the soluble p75 TNF receptor molecule etanercept, that has recently been approved by the FDA for the treatment of patients with early RA. Phase 2 of this study will be initiated upon access to etanercept and completion of Phase I of the study. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Healthy
• Rheumatoid Arthritis

• NCT number: NCT00034060
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 2
• Start date: April 2002
• Completion date: December 2005