Glucose HomeostasisNCT01143493
The Role of Glucocorticoid Receptor SNPs in Receptor Function and Metabolic Disease
An observational study of Glucose Homeostasis and Protein Metabolism, run by National Institute of Environmental Health Sciences (NIEHS) at 1 site in United States.
Trial summary
Background: Glucocorticoids are primary stress response hormones released from the adrenal gland when an individual is under stress. Chronic or ongoing elevation of these hormones due to prolonged stress or medical treatments can have numerous harmful effects. Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Glucose Homeostasis, Protein Metabolism, Lipid Metabolism
- How many people
- 278 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2010to 2 Dec 2019
- Phase
- Observational
- 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 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female 18 years of age or older at the time of enrollment
- Must be a participant in the EPR study
- Are genotyped and determined to be heterozygote or homozygote carriers of one of the two hGR SNPs (hGR9B A3669G and hGR N363S) or are wild type at the SNP location
- Able to understand and provide written informed consent to participate in the study
- Able to travel to the CRU
- Willing and able to fast for periods of up to 12 hours during the study
- Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. If the individual has a chronic condition such as diabetes or high blood pressure, healthy also means that they are being treated and the condition is under control).
Who cannot join
- Participants with the following history will be excluded from part 1 of the study:
- Any glucocorticoid use within approximately 14 days of scheduled visit 1 including oral, inhaled, nasal sprays, and cream (dermal/mucosal)
- Pregnant or currently breastfeeding
- Planning to use certain medications because they can affect test results.
- Any condition that, in the investigator's opinion, places the participant at undue risk for complications.
- Participants with the following history will be excluded from part 2 of the study to avoid confounding the dexamethasone suppression test:
Show all 21Show fewer
- Any glucocorticoid use within approximately 14 days of scheduled visit 2 including oral, inhaled, nasal sprays, and cream (dermal/mucosal)
- Pregnant or currently breastfeeding
- Currently enrolled in another clinical research study and/or is receiving an investigational agent for any reason
- Does not agree to take dexamethasone at scheduled time
- Planning to use certain medications such as corticosteroids, estrogens, or tetracyclines prior to the visit 2, because they can affect test results. If the participant is willing to withhold these medications for 14 days, then the participant will be allowed to participate in visit 2.
- Participants with the following history will be excluded from part 2 of the study because the dexamethasone may cause potential harm to the participant:
- High blood pressure of 160/10 mm Hg or above.
- Active coronary artery disease (angina) or moderate to severe heart failure stage New York Heart Association III-IV
- Renal failure
- Glaucoma
- Uncontrolled psychiatric disorders such as bipolar disorder or schizoaffective disorder
- Active systemic fungal infection
- Prior hypersensitivity reaction to Dexamethasone
- Currently receiving treatment for cancer (certain cancers, like lung cancer make adrenocorticotropic hormone (ACTH), and all induce stress)
- Any condition that, in the investigator's opinion, places the participant at undue risk for complications
Trial locations and contacts
1 site in 1 country.
United States1 site
NIEHS Clinical Research Unit (CRU)
Research Triangle Park, North Carolina
About this study
Background:
- Glucocorticoids are primary stress response hormones released from the adrenal gland when an individual is under stress. Chronic or ongoing elevation of these hormones due to prolonged stress or medical treatments can have numerous harmful effects. Researchers are interested in learning more about how these hormones affect cell growth, development, and death. To study glucocorticoid hormones, researchers plan to use the medication dexamethasone, which affects the parts of cells that respond to glucocorticoid hormones.
Read more
Objectives:
- To study glucocorticoid stress hormones in healthy individuals before and after receiving dexamethasone.
Eligibility:
- Healthy individuals at least 18 years of age.
- Participants must not be using certain medications that may affect the dexamethasone test, including hormonal contraception, steroid-based drugs, and some antidepressants.
Design:
- This study will require an initial screening visit and a second study visit. The visits are estimated to require about 1 to 2 hours of participation over a period of up to 14 days.
- Participants will be screened at visit 1 with a full physical examination and medical history, and an initial blood sample for testing.
- For visit 2, participants will be asked to abstain from all food and drinks except for water for 12 hours before the appointment, and will take one tablet of dexamethasone 9 hours before the appointment.
- Participants will have a second blood sample taken during visit 2, and will receive a snack after the blood is drawn.
Read the detailed description
STUDY DESIGN:
This in vivo and in vitro observational gene association study will investigate the functional relevance of SNPs in the NR3C1 gene in selected populations. A subgroup of the EPR will be genotyped to identify novel SNPs in the NR3C1 gene. The most promising SNPs for functional relevance in in vitro assays will be examined. Individuals with and without functionally relevant, novel SNPs will be recruited for further study. In part 1, lymphocytes from these participants will be isolated, exposed ex vivo to corticosteroids, and gene expression profiles in response to this stimulus will be compared. In part 2, in vivo effect of these SNPs in steroid responsiveness will be evaluated by performing a modified low dose dexamethasone suppression test comparing by genotype. The study design is innovative as a gene association study in the sense that participants are recruited on the basis of genotype and then the phenotype of each participant is observed.
STUDY DURATION:
It is anticipated that the study will require 48 months to complete participants study visits.
PRIMARY OBJECTIVE:
Investigate in vivo the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in steroid responsiveness by performing a modified dexamethasone suppression test and comparing responses by genotype.
SECONDARY OBJECTIVE:
Investigate the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in human steroid responsiveness by comparing (across genotypes) gene expression profiles of isolated macrophages and lymphocytes exposed ex vivo to corticosteroids.
PRIMARY ENDPOINT:
Measure the change in serum cortisol levels after modified dexamethasone suppression test.
SECONDARY ENDPOINT:
Measure gene expression fold changes by microarray analysis after ex vivo glucocorticoid exposure of macrophages and lymphocytes; validation of affected RNA (elevated or decreased expression) through PCR analysis.
- Conditions
- Glucose Homeostasis, Protein Metabolism, Lipid Metabolism, Respiratory Function, Connective Tissue Metabolism
- Keywords
- Genetic Polymorphism, Glucocorticoid, Health Volunteer, HV
- Medical subject headings
- Respiratory Aspiration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Carrier - Other | Not described | |
| Carrier hGR N363S Heterozygote | Not described | |
| Carrier hGR N363S Homozygote | Not described | |
| Carrier hGR9B A3669G Heterozygote | Not described | |
| Carrier hGR9B A3669G Homozygote | Not described | |
| Control | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure the change in serum cortisol levels after modified dexamethasone suppression test
The null hypothesis for this endpoint (primary hypothesis for this study) is that there is no difference among genotypes in the change from baseline cortisol level. The two-sided alternative hypothesis is that there is a trend(homozygous wild-type to heterozygous to homozygous for the minor allele) in change from baseline.
Measured: baseline level in first visit, posttreatment level in second visit
Secondary outcomes (1)
Measure gene expression fold changes by microarray analysis after ex vivo glucocorticoid exposure of macrophages and lymphocytes; validation of affected RNA (elevated or decreased expression) through PCR analysis.
The secondary null hypotheses are that there are no differences among genotypes in fold-change for expression level (measured by RT-PCR for the genes selected by the microarray analysis as having differential expression), and the two-sided alternative is that there are trends.
Measured: The cells are cultured from blood drawn from participants at the first clinic visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2010 (estimated)
- Study start30 Sep 2010
- Primary completion2 Dec 2019
- Study completion2 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Glucose HomeostasisStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 278 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Stavros Garantziotis, M.D., Principal investigator, National Institute of Environmental Health Sciences (NIEHS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01143493
- Sponsor's protocol ID
- 100130
- Other IDs
- 10-E-0130
- Status last verified
- Dec 2019
- First submitted
- 11 Jun 2010
- Last updated
- 4 Dec 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23. doi: 10.1056/NEJMra050541. No abstract available.
PubMed 16236742DeRijk RH, Schaaf M, de Kloet ER. Glucocorticoid receptor variants: clinical implications. J Steroid Biochem Mol Biol. 2002 Jun;81(2):103-22. doi: 10.1016/s0960-0760(02)00062-6.
PubMed 12137800Huizenga NA, Koper JW, de Lange P, Pols HA, Stolk RP, Grobbee DE, de Jong FH, Lamberts SW. Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals. J Clin Endocrinol Metab. 1998 Jan;83(1):47-54. doi: 10.1210/jcem.83.1.4498.
PubMed 9435415
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Glucocorticoid Receptor SNPs in Receptor Function and Metabolic Disease
- ClinicalTrials.gov ID
- NCT01143493
- Acronym / sponsor ID
- 100130
- Conditions
- Glucose Homeostasis, Protein Metabolism, Lipid Metabolism, Respiratory Function, Connective Tissue Metabolism
- Keywords
- Genetic Polymorphism, Glucocorticoid, Health Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 278 participants (actual)
- Lead sponsor
- National Institute of Environmental Health Sciences (NIEHS)US National Institutes of Health
- Study start
- 30 Sep 2010
- Primary completion
- 2 Dec 2019 (actual)
- Study completion
- 2 Dec 2019 (actual)
- First posted
- 14 Jun 2010 (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.
Background:
- Glucocorticoids are primary stress response hormones released from the adrenal gland when an individual is under stress. Chronic or ongoing elevation of these hormones due to prolonged stress or medical treatments can have numerous harmful effects. Researchers are interested in learning more about how these hormones affect cell growth, development, and death. To study glucocorticoid hormones, researchers plan to use the medication dexamethasone, which affects the parts of cells that respond to glucocorticoid hormones.
Objectives:
- To study glucocorticoid stress hormones in healthy individuals before and after receiving dexamethasone.
Eligibility:
- Healthy individuals at least 18 years of age.
- Participants must not be using certain medications that may affect the dexamethasone test, including hormonal contraception, steroid-based drugs, and some antidepressants.
Design:
- This study will require an initial screening visit and a second study visit. The visits are estimated to require about 1 to 2 hours of participation over a period of up to 14 days.
- Participants will be screened at visit 1 with a full physical examination and medical history, and an initial blood sample for testing.
- For visit 2, participants will be asked to abstain from all food and drinks except for water for 12 hours before the appointment, and will take one tablet of dexamethasone 9 hours before the appointment.
- Participants will have a second blood sample taken during visit 2, and will receive a snack after the blood is drawn.
Detailed description
STUDY DESIGN:
This in vivo and in vitro observational gene association study will investigate the functional relevance of SNPs in the NR3C1 gene in selected populations. A subgroup of the EPR will be genotyped to identify novel SNPs in the NR3C1 gene. The most promising SNPs for functional relevance in in vitro assays will be examined. Individuals with and without functionally relevant, novel SNPs will be recruited for further study. In part 1, lymphocytes from these participants will be isolated, exposed ex vivo to corticosteroids, and gene expression profiles in response to this stimulus will be compared. In part 2, in vivo effect of these SNPs in steroid responsiveness will be evaluated by performing a modified low dose dexamethasone suppression test comparing by genotype. The study design is innovative as a gene association study in the sense that participants are recruited on the basis of genotype and then the phenotype of each participant is observed.
STUDY DURATION:
It is anticipated that the study will require 48 months to complete participants study visits.
PRIMARY OBJECTIVE:
Investigate in vivo the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in steroid responsiveness by performing a modified dexamethasone suppression test and comparing responses by genotype.
SECONDARY OBJECTIVE:
Investigate the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in human steroid responsiveness by comparing (across genotypes) gene expression profiles of isolated macrophages and lymphocytes exposed ex vivo to corticosteroids.
PRIMARY ENDPOINT:
Measure the change in serum cortisol levels after modified dexamethasone suppression test.
SECONDARY ENDPOINT:
Measure gene expression fold changes by microarray analysis after ex vivo glucocorticoid exposure of macrophages and lymphocytes; validation of affected RNA (elevated or decreased expression) through PCR analysis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Carrier - Other | – | – |
| Carrier hGR N363S Heterozygote | – | – |
| Carrier hGR N363S Homozygote | – | – |
| Carrier hGR9B A3669G Heterozygote | – | – |
| Carrier hGR9B A3669G Homozygote | – | – |
| Control | – | – |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female 18 years of age or older at the time of enrollment
- Must be a participant in the EPR study
- Are genotyped and determined to be heterozygote or homozygote carriers of one of the two hGR SNPs (hGR9B A3669G and hGR N363S) or are wild type at the SNP location
- Able to understand and provide written informed consent to participate in the study
- Able to travel to the CRU
Key exclusion criteria (21 listed)
- Any glucocorticoid use within approximately 14 days of scheduled visit 1 including oral, inhaled, nasal sprays, and cream (dermal/mucosal)
- Pregnant or currently breastfeeding
- Planning to use certain medications because they can affect test results.
- Any condition that, in the investigator's opinion, places the participant at undue risk for complications.
- Participants with the following history will be excluded from part 2 of the study to avoid confounding the dexamethasone suppression test:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Measure the change in serum cortisol levels after modified dexamethasone suppression test
Time frame: baseline level in first visit, posttreatment level in second visit
The null hypothesis for this endpoint (primary hypothesis for this study) is that there is no difference among genotypes in the change from baseline cortisol level. The two-sided alternative hypothesis is that there is a trend(homozygous wild-type to heterozygous to homozygous for the minor allele) in change from baseline.
1 secondary outcome
Measure gene expression fold changes by microarray analysis after ex vivo glucocorticoid exposure of macrophages and lymphocytes; validation of affected RNA (elevated or decreased expression) through PCR analysis.
Time frame: The cells are cultured from blood drawn from participants at the first clinic visit.
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 Dec 2019.
- Background: PubMed 16236742Rhen T, Cidlowski JA. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N Engl J Med. 2005 Oct 20;353(16):1711-23. doi: 10.1056/NEJMra050541. No abstract available.
- Background: PubMed 12137800DeRijk RH, Schaaf M, de Kloet ER. Glucocorticoid receptor variants: clinical implications. J Steroid Biochem Mol Biol. 2002 Jun;81(2):103-22. doi: 10.1016/s0960-0760(02)00062-6.
- Background: PubMed 9435415Huizenga NA, Koper JW, de Lange P, Pols HA, Stolk RP, Grobbee DE, de Jong FH, Lamberts SW. Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals. J Clin Endocrinol Metab. 1998 Jan;83(1):47-54. doi: 10.1210/jcem.83.1.4498.
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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.
Stavros Garantziotis, M.D. principal investigator
National Institute of Environmental Health Sciences (NIEHS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Glucose Homeostasis and Protein Metabolism, run by National Institute of Environmental Health Sciences (NIEHS) 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 7 inclusion and 21 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 Dec 2019. 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.
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?
Measure the change in serum cortisol levels after modified dexamethasone suppression test (time frame: baseline level in first visit, posttreatment level in second visit). 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 NCT01143493, which also lists 3 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 Dec 2019.