Rheumatoid ArthritisPhase 2NCT00034060
The Role of Cytokines on Growth Hormone Suppression in Premenopausal Women With Rheumatoid Arthritis and the Effect of Treatment With Etanercept
A Phase 2 study testing Etanercept in people with Rheumatoid Arthritis and Healthy, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis, Healthy
- What is being tested?
- Etanercept
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2002to Dec 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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.
- 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.
Who cannot join
- 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
Show all 13Show fewer
- 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.
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the detailed 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.
- Conditions
- Rheumatoid Arthritis, Healthy
- Being tested
- Etanercept
- Keywords
- Cytokines, Exanercept, Cachexia, Body Composition, Vascular Endothelial System, Rheumatoid Arthritis, RA, Women, Healthy Volunteer, HV, Normal Control
- Medical subject headings
- Arthritis, Rheumatoid, Cachexia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtanerceptDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2002 (estimated)
- Study startApr 2002
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 36 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00034060
- Sponsor's protocol ID
- 020170
- Other IDs
- 02-AR-0170
- Status last verified
- Dec 2005
- First submitted
- 19 Apr 2002
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
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. No abstract available. Italian.
PubMed 1145019Straub 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. doi: 10.1002/1529-0131(200103)44:33.0.CO;2-U.
PubMed 11263762Gabriel 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.
PubMed 10606358Blackman MR, Muniyappa R, Wilson M, Moquin BE, Baldwin HL, Wong KA, Snyder C, Magalnick M, Alli S, Reynolds J, Steinberg SM, Goldbach-Mansky R. Diurnal secretion of growth hormone, cortisol, and dehydroepiandrosterone in pre- and perimenopausal women with active rheumatoid arthritis: a pilot case-control study. Arthritis Res Ther. 2007;9(4):R73. doi: 10.1186/ar2271.
PubMed 17662149
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Suppression of the Growth Hormone/ Insulin-Like Growth Factor-1 (GH/IGF-1) Axis in Women With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT00034060
- Acronym / sponsor ID
- 020170
- Conditions
- Rheumatoid Arthritis, Healthy
- Keywords
- Cytokines, Exanercept, Cachexia, Body Composition, Vascular Endothelial System, Rheumatoid Arthritis, RA, Women
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)US National Institutes of Health
- Study start
- Apr 2002
- Study completion
- Dec 2005
- First posted
- 22 Apr 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
- Primary purpose
- Treatment
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Etanercept | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 1145019Mancia 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. No abstract available. Italian.
- Background: PubMed 11263762Straub 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. doi: 10.1002/1529-0131(200103)44:33.0.CO;2-U.
- Background: PubMed 10606358Gabriel 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.
- Derived from this study: PubMed 17662149Blackman MR, Muniyappa R, Wilson M, Moquin BE, Baldwin HL, Wong KA, Snyder C, Magalnick M, Alli S, Reynolds J, Steinberg SM, Goldbach-Mansky R. Diurnal secretion of growth hormone, cortisol, and dehydroepiandrosterone in pre- and perimenopausal women with active rheumatoid arthritis: a pilot case-control study. Arthritis Res Ther. 2007;9(4):R73. doi: 10.1186/ar2271.
Related trials for Rheumatoid Arthritis
RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Etanercept in people with Rheumatoid Arthritis and Healthy, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00034060, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.