Healthy Clinical Trial
Official title:
Suppression of the Growth Hormone/ Insulin-Like Growth Factor-1 (GH/IGF-1) Axis in Women With Rheumatoid Arthritis
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.
Status | Completed |
Enrollment | 36 |
Est. completion date | December 2005 |
Est. primary completion date | |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Female |
Age group | N/A and older |
Eligibility |
INCLUSION CRITERIA - General: Healthy women, or women with RA, 18-55 year old, with a history of regular menses or who are perimenopausal, have a BMI less than 30, able to provide informed consent to all aspects of the study after full information is provided. Women must have a negative pregnancy test at screening. Study participants will be allowed to continue taking medications for chronic, stable conditions, such as hypertension and hypercholesteremia, while in the study. INCLUSION CRITERIA - for RA Patients: Active RA as defined by 9 tender and 6 swollen joints; ESR greater than 35 mm/hr OR CRP greater than 2.0 mg/dL; and, morning stiffness greater than 45 min. Actively menstruating with a normal estrogen level or who are perimenopausal. Women must be practicing, or willing to practice, an acceptable method of birth control that does not involve use of prescription or OTC estrogen/progesterone preparations during the two weeks prior to screening. Acceptable means of contraception include: abstinence, barrier methods with spermicides, intrauterine devices (IUD's) or surgical sterilization. (phase 2 of the study only) Current use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or hydroxychloroquine are permitted. Drug doses must have been stable for at least one month prior to enrollment, and must be held constant during the study unless toxicity requires dose reduction. Past use of a disease modifying agent (DMARD) such as methotrexate, sulfasalazine and cyclosporine is allowed. EXCLUSION CRITERIA - General: Patients or control subject will be excluded if they exhibit any medical condition that has the potential of placing the candidate at unnecessary risk during the study. Additionally, patients with impaired renal, hepatic, cardiovascular or endocrine-metabolic function, or any immunodeficiency syndrome including HIV infection, will be excluded Use of systemic corticosteroids in the two weeks before screening and study entry. Women with a history of cancer, with the exception of limited, resolved skin cancer. Women who are menopausal. Clinical menopause is defined as the absence of spontaneous menses during the preceding 12 months. Pregnant women or women who are nursing. Use of prescription or OTC estrogen/progesterone preparations during the two weeks prior to screening The patient or control subject has received any investigational drug within 30 days of the start of the study. History of autoimmune endocrinopathy. Serious medical illnesses or abnormal laboratory values that would, in the opinion of the P.I., preclude study participation. EXCLUSION CRITERIA - For RA Patients: BMI greater than or equal to 30. Active infection or other contraindication to use of an anti-TNF agent (phase 2 of the study only). History of untreated tuberculosis, or of a positive PPD without completion of adequate treatment. (phase 2 of the study only) Live vaccinations in the 3 months prior to study (phase 2 of the study only). |
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) |
United States,
Gabriel SE, Crowson CS, O'Fallon WM. Mortality in rheumatoid arthritis: have we made an impact in 4 decades? J Rheumatol. 1999 Dec;26(12):2529-33. — View Citation
Mancia D, Lechi A, Terzano MG, Gemignani F, Vigouroux PR, Naquet R. [Electrophysiological criteria and prognostic evaluation in prolonged post-traumatic coma. Joint study of 150 cases]. Riv Neurol. 1975 Jan-Mar;45(1):44-59. Italian. — View Citation
Straub RH, Cutolo M. Involvement of the hypothalamic--pituitary--adrenal/gonadal axis and the peripheral nervous system in rheumatoid arthritis: viewpoint based on a systemic pathogenetic role. Arthritis Rheum. 2001 Mar;44(3):493-507. Review. — View Citation
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