Metabolic Syndrome XPhase 2/3NCT00111956
Effects of Tumor Necrosis Factor (TNF)-Alpha Antagonism in Patients With Metabolic Syndrome
A Phase 2/3 study testing Etanercept in people with Metabolic Syndrome X, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Metabolic syndrome is associated with increased inflammatory cytokines and reduced adiponectin, that may be mediated in part by TNF production from abdominal fat. We reasoned that an anti-TNF agent would reduce C-reactive protein (CRP) and increase adiponectin, improving the inflammatory milieu associated with… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Metabolic Syndrome X
- What is being tested?
- Etanercept
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2004to May 2005
- Phase
- Phase 2/3
- 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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Hyperinsulinemia in the upper quartile of the non-diabetic population defined as ≥10 mU/mL (Framingham Data, oral communication, James Meigs, MD) or fasting glucose 110-126 mg/dL, plus two of the following: *Abdominal obesity defined by waist hip ratio > 0.90 for men and > 0.85 for women or *body mass index (BMI) > 30 kg/m2
- Dyslipidemia including serum triglycerides ≥150 mg/dl or serum HDL < 0.9 mmol/L for men (35 mg/dL) and < 1.0 mmol/L (39 mg/dL) for women
- Hypertension defined as blood pressure ≥ 140/90 or on medication
Who cannot join
- Positive PPD (≥ 5mm induration) on screening
- Current infection
- Therapy with glucocorticoid or immunosuppressant at time of recruitment or within past 3 months
- Reception of live vaccine within 1 week of recruitment
- History of blood dyscrasia including any kind of anemia, thrombocytopenia, pancytopenia. Women with a reversible cause of anemia that has resolved will be eligible.
- History of malignancy (except patients with surgically cured basal cell or squamous cell skin cancers who will be eligible)
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- History of organ transplantation
- History of central nervous system (CNS) demyelinating disorder or any first degree relative with multiple sclerosis
- History of congestive heart failure (CHF) classes I-IV
- Current use of insulin, any oral anti-hyperglycemic agents, pentoxyfylline, beta-agonists
- Current use of fibrate or niacin
- Initiation of statin therapy within prior 6 weeks or expecting a change in statin dose over the upcoming 3 months
- Hemoglobin < 11 g/dl
- Positive pregnancy test
- Women of child-bearing potential not currently using non-hormonal birth control methods including barrier methods (intrauterine device (IUD), condoms, diaphragms) or abstinence
- Patients with known autoimmune or inflammatory conditions
Trial locations and contacts
1 site in 1 country.
About this study
Metabolic syndrome is associated with increased inflammatory cytokines and reduced adiponectin, that may be mediated in part by TNF production from abdominal fat. We reasoned that an anti-TNF agent would reduce C-reactive protein (CRP) and increase adiponectin, improving the inflammatory milieu associated with metabolic syndrome.
Read the detailed description
Screening visit 1:
Fifty six patients will be randomized to receive etanercept or identical placebo. During the screening visit, after informed consent is obtained, subjects will undergo a medical history and physical exam, which will include vital signs, weight, abdominal girth measurements and an evaluation for signs of underlying infection. A purified protein derivative (PPD) of 5 tuberculin units (TU) (0.1 milliliter of 5 TU/0.1 ml solution) will be intradermally placed to test for the presence of tuberculosis (TB). Fasting blood work will include a complete blood count (CBC), glucose, insulin, a cholesterol panel, and urine pregnancy test. Subjects will be shown what a subcutaneous injection entails using placebo. Patients will be selected based on their laboratory results, abdominal girth measurements and PPD negativity 48 hrs after placement.
Screening visit 2:
Subjects will return 48 hours after their first screening visit for evaluation of their PPD test. In the event of a positive PPD, subjects will be excluded from the study, and their primary care physicians will be notified of their test result.
Day 1 visit:
Subjects will report to Massachusetts General Hospital (MGH) or Massachusetts Institute of Technology (MIT) Clinical Research Center (GCRC) after an overnight fast. Fasting blood work will be obtained to test for CRP, adiponectin, IL-6, TNF-alpha, TNF-alpha receptor 1, TNF-alpha receptor 2, free fatty acids, glucose, insulin and a cholesterol panel, and CBC. A urine pregnancy test will be done. Patients will be asked to recall the food they consumed over the past 24 hours. A bionutritionist will measure height, weight, waist, hip, chest, arm, neck and thigh circumference. Subjects will be instructed to practice adequate birth control throughout the study. Serum will be stored for etanercept antibody testing.
Subjects will then undergo an insulin modified frequently sampled intravenous (IV) glucose tolerance test (FSIGT) as initially developed by Bergman et al.
Dual energy x-ray absorptiometry (DEXA) (Hologic QDR 4500) will be used to determine whole body and regional fat. The technique has a precision error (1 SD) of 3% for whole body fat and 1.5% for lean mass. Subjects will also undergo a single thin-slice CT scan of the abdomen at L4 vertebral body to determine visceral and subcutaneous fat area.
Indirect calorimetry for the measurement of resting energy expenditure indirect calorimetry using the Deltatrac instrument (Sensormedics, Anaheim, CA) will be carried out.
Drug administration:
Patients will be given a total of either etanercept 50 mg subcutaneously or placebo subcutaneously at the GCRC at the end of their visit. They will receive this in two injections of 25 mg each, one given immediately following the other, at different body sites. Etanercept will be supplied as a sterile, white, preservative-free, lyophilized powder. The pharmacy will reconstitute it with 1 mL of the supplied sterile bacteriostatic water for injection (BWFI), United States Pharmacopeia (USP) (containing 0.9% benzyl alcohol). Each vial of etanercept contains 25 mg etanercept, 40 mg mannitol, 10 mg sucrose, and 1.2 mg tromethamine. Subjects will receive the 50 mg dose of etanercept or placebo once a week, given as two 25 mg injections, one immediately following the other, at different body sites, at each of their ensuing three visits to the GCRC, on Visit Day 8, Visit Day 15 and Visit Day 22. Subjects will be monitored for 30 minutes after the injection of study drug at each visit. The skin injection site will be observed and their vital signs will be taken. If a subject has a significant exposure to varicella virus during the study, transient termination of the study will be considered.
Day 8 visit, Day 15 visit, Day 22 visit:
Subjects will report to MGH or MIT Clinical Research Center after an overnight fast. Each subject will undergo a history and physical exam to assess for safety and compliance. Fasting blood work will be obtained. A bionutritionist will measure subjects' height, weight, hip and waist circumference and calculate a waist to hip ratio. They will receive 50 mg of either etanercept or placebo, given as two 25 mg doses subcutaneously, at different body sites.
Day 25 visit:
Subjects will report to MGH or MIT Clinical Research Center after an overnight fast. Each subject will undergo a history and physical exam to assess for safety and compliance. Blood work, a urine pregnancy test and 24 hour food recall will be collected, identical to that on Day 1 visit. Anthropomorphic measurements will be the same as the Day 1 visit. Subjects will undergo an intravenous glucose tolerance test (IVGTT) identical to that on the Day 1 visit. Subjects will undergo a DEXA, bioelectric impedance analysis (BIA), and CT, and indirect calorimetry identical to those on the Day 1 visit. No study drug will be administered at this visit.
- Conditions
- Metabolic Syndrome X
- Being tested
- Etanercept, Placebo
- Keywords
- TNF, metabolic syndrome, inflammation, CRP, adiponectin
- Medical subject headings
- Metabolic Syndrome, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtanerceptDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Etanercept | Experimental | Not described Receives: Drug: Etanercept |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
C-reactive protein (CRP), mg/L
Measured: 25 days
Secondary outcomes (4)
Adiponectin, ug/mL
Measured: 25 days
Interleukin 6, ng/L
Measured: 25 days
Fibrinogen, mg/dL
Measured: 25 days
Insulin sensitivity
Measured: 25 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2005 (estimated)
- Study startApr 2004
- Primary completionMay 2005
- Study completionMay 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metabolic Syndrome XStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Massachusetts General Hospital
- Responsible party
- Sponsor
- Investigators
- Steven K Grinspoon, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00111956
- Sponsor's protocol ID
- TNF-alpha (completed)
- Other IDs
- F32DK068902
- Status last verified
- Oct 2017
- First submitted
- 26 May 2005
- Last updated
- 6 Oct 2017
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Bernstein LE, Berry J, Kim S, Canavan B, Grinspoon SK. Effects of etanercept in patients with the metabolic syndrome. Arch Intern Med. 2006 Apr 24;166(8):902-8. doi: 10.1001/archinte.166.8.902.
PubMed 16636217
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Tumor Necrosis Factor (TNF)-Alpha Antagonism in Patients With Metabolic Syndrome
- ClinicalTrials.gov ID
- NCT00111956
- Acronym / sponsor ID
- TNF-alpha (completed)
- Conditions
- Metabolic Syndrome X
- Keywords
- TNF, metabolic syndrome, inflammation, CRP, adiponectin
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- Massachusetts General Hospital
- Study start
- Apr 2004 (actual)
- Primary completion
- May 2005 (actual)
- Study completion
- May 2005 (actual)
- First posted
- 27 May 2005 (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.
Metabolic syndrome is associated with increased inflammatory cytokines and reduced adiponectin, that may be mediated in part by TNF production from abdominal fat. We reasoned that an anti-TNF agent would reduce C-reactive protein (CRP) and increase adiponectin, improving the inflammatory milieu associated with metabolic syndrome.
Detailed description
Screening visit 1:
Fifty six patients will be randomized to receive etanercept or identical placebo. During the screening visit, after informed consent is obtained, subjects will undergo a medical history and physical exam, which will include vital signs, weight, abdominal girth measurements and an evaluation for signs of underlying infection. A purified protein derivative (PPD) of 5 tuberculin units (TU) (0.1 milliliter of 5 TU/0.1 ml solution) will be intradermally placed to test for the presence of tuberculosis (TB). Fasting blood work will include a complete blood count (CBC), glucose, insulin, a cholesterol panel, and urine pregnancy test. Subjects will be shown what a subcutaneous injection entails using placebo. Patients will be selected based on their laboratory results, abdominal girth measurements and PPD negativity 48 hrs after placement.
Screening visit 2:
Subjects will return 48 hours after their first screening visit for evaluation of their PPD test. In the event of a positive PPD, subjects will be excluded from the study, and their primary care physicians will be notified of their test result.
Day 1 visit:
Subjects will report to Massachusetts General Hospital (MGH) or Massachusetts Institute of Technology (MIT) Clinical Research Center (GCRC) after an overnight fast. Fasting blood work will be obtained to test for CRP, adiponectin, IL-6, TNF-alpha, TNF-alpha receptor 1, TNF-alpha receptor 2, free fatty acids, glucose, insulin and a cholesterol panel, and CBC. A urine pregnancy test will be done. Patients will be asked to recall the food they consumed over the past 24 hours. A bionutritionist will measure height, weight, waist, hip, chest, arm, neck and thigh circumference. Subjects will be instructed to practice adequate birth control throughout the study. Serum will be stored for etanercept antibody testing.
Subjects will then undergo an insulin modified frequently sampled intravenous (IV) glucose tolerance test (FSIGT) as initially developed by Bergman et al.
Dual energy x-ray absorptiometry (DEXA) (Hologic QDR 4500) will be used to determine whole body and regional fat. The technique has a precision error (1 SD) of 3% for whole body fat and 1.5% for lean mass. Subjects will also undergo a single thin-slice CT scan of the abdomen at L4 vertebral body to determine visceral and subcutaneous fat area.
Indirect calorimetry for the measurement of resting energy expenditure indirect calorimetry using the Deltatrac instrument (Sensormedics, Anaheim, CA) will be carried out.
Drug administration:
Patients will be given a total of either etanercept 50 mg subcutaneously or placebo subcutaneously at the GCRC at the end of their visit. They will receive this in two injections of 25 mg each, one given immediately following the other, at different body sites. Etanercept will be supplied as a sterile, white, preservative-free, lyophilized powder. The pharmacy will reconstitute it with 1 mL of the supplied sterile bacteriostatic water for injection (BWFI), United States Pharmacopeia (USP) (containing 0.9% benzyl alcohol). Each vial of etanercept contains 25 mg etanercept, 40 mg mannitol, 10 mg sucrose, and 1.2 mg tromethamine. Subjects will receive the 50 mg dose of etanercept or placebo once a week, given as two 25 mg injections, one immediately following the other, at different body sites, at each of their ensuing three visits to the GCRC, on Visit Day 8, Visit Day 15 and Visit Day 22. Subjects will be monitored for 30 minutes after the injection of study drug at each visit. The skin injection site will be observed and their vital signs will be taken. If a subject has a significant exposure to varicella virus during the study, transient termination of the study will be considered.
Day 8 visit, Day 15 visit, Day 22 visit:
Subjects will report to MGH or MIT Clinical Research Center after an overnight fast. Each subject will undergo a history and physical exam to assess for safety and compliance. Fasting blood work will be obtained. A bionutritionist will measure subjects' height, weight, hip and waist circumference and calculate a waist to hip ratio. They will receive 50 mg of either etanercept or placebo, given as two 25 mg doses subcutaneously, at different body sites.
Day 25 visit:
Subjects will report to MGH or MIT Clinical Research Center after an overnight fast. Each subject will undergo a history and physical exam to assess for safety and compliance. Blood work, a urine pregnancy test and 24 hour food recall will be collected, identical to that on Day 1 visit. Anthropomorphic measurements will be the same as the Day 1 visit. Subjects will undergo an intravenous glucose tolerance test (IVGTT) identical to that on the Day 1 visit. Subjects will undergo a DEXA, bioelectric impedance analysis (BIA), and CT, and indirect calorimetry identical to those on the Day 1 visit. No study drug will be administered at this visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Etanercept | Experimental | Drug: Etanercept |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Hyperinsulinemia in the upper quartile of the non-diabetic population defined as ≥10 mU/mL (Framingham Data, oral communication, James Meigs, MD) or fasting glucose 110-126 mg/dL, plus two of the following: *Abdominal obesity defined by waist hip ratio > 0.90 for men and > 0.85 for women or *body mass index (BMI) > 30 kg/m2
- Dyslipidemia including serum triglycerides ≥150 mg/dl or serum HDL < 0.9 mmol/L for men (35 mg/dL) and < 1.0 mmol/L (39 mg/dL) for women
- Hypertension defined as blood pressure ≥ 140/90 or on medication
Key exclusion criteria (16 listed)
- Positive PPD (≥ 5mm induration) on screening
- Current infection
- Therapy with glucocorticoid or immunosuppressant at time of recruitment or within past 3 months
- Reception of live vaccine within 1 week of recruitment
- History of blood dyscrasia including any kind of anemia, thrombocytopenia, pancytopenia. Women with a reversible cause of anemia that has resolved will be eligible.
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 | Etanercept |
| Placebo | Drug | Placebo |
Primary outcome
C-reactive protein (CRP), mg/L
Time frame: 25 days
4 secondary outcomes
Adiponectin, ug/mL
Time frame: 25 days
Interleukin 6, ng/L
Time frame: 25 days
Fibrinogen, mg/dL
Time frame: 25 days
Insulin sensitivity
Time frame: 25 days
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 6 Oct 2017.
- Results publication: PubMed 16636217Bernstein LE, Berry J, Kim S, Canavan B, Grinspoon SK. Effects of etanercept in patients with the metabolic syndrome. Arch Intern Med. 2006 Apr 24;166(8):902-8. doi: 10.1001/archinte.166.8.902.
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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.
Steven K Grinspoon, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Etanercept in people with Metabolic Syndrome X, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 3 inclusion and 16 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 6 Oct 2017. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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.
What does the primary outcome measure?
C-reactive protein (CRP), mg/L (time frame: 25 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00111956, which also lists 1 linked publication.
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 6 Oct 2017.