Adrenal SufficiencyNCT00196001
Adrenocorticotropic Hormone (ACTH) Stimulation and G Protein
An observational study of Adrenal Sufficiency, run by Children's Mercy Hospital Kansas City at 1 site in United States.
Trial summary
Males and females may exhibit different responses to testing of adrenal function. The hormones responsible for controlling adrenal function are ACTH (adrenocorticotropic hormone or corticotropin) and CRH (corticotropin-releasing hormone). Adrenal function is tested with an ACTH stimulation test. Read more about this study
- Who is it for?
- Ages 6 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Adrenal Sufficiency
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2005to Apr 2013
- 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 6 to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: Healthy male and female subjects (ages 6-34)
Who may be able to join
- Healthy males and females aged 6-60
Who cannot join
- Known medical condition
- Use of inhaled, topical, or oral steroids
- Use of oral contraceptive pills or hormone replacement
- Menopause
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Mercy Hospital
Kansas City, Missouri, 64108
About this study
Official title: G Protein Expression in Response to ACTH Stimulation Testing
Males and females may exhibit different responses to testing of adrenal function. The hormones responsible for controlling adrenal function are ACTH (adrenocorticotropic hormone or corticotropin) and CRH (corticotropin-releasing hormone). Adrenal function is tested with an ACTH stimulation test. ACTH stimulates the adrenal glands to produce cortisol. Cortisol levels are measured, and a certain peak level indicates normal adrenal gland function. Females may produce more cortisol in response to ACTH testing than males. This difference may be due to certain proteins, called G proteins. The hormones controlling adrenal function, ACTH and CRH, work through G proteins. Females may have more G proteins than males allowing for the increased cortisol response to ACTH stimulation.
The investigators speculate that:
Read more
- There may be differences in adrenal responsiveness to ACTH stimulation testing between healthy males and females.
- ACTH and CRH induce their own function.
- Sex differences in adrenal responsiveness to ACTH stimulation testing may be related to sex differences in G protein expression.
In this study, cortisol, a hormone produced by the adrenal glands, will be measured before and after the administration of ACTH.
This study will also measure G proteins. G proteins are found in the white blood cells. White blood cells from females may have more active G proteins than white blood cells from males. Sex differences may be augmented after exposure to ACTH.
Read the detailed description
Many nonsteroidal hormones work through G protein signal transducers. These heterotrimeric signal transducers couple cell surface receptors to intracellular pathways, thus conveying biologic effects. Most hormones that work via the stimulatory G protein, Gas, also exert actions through a homologous stimulatory G protein, Gaq, suggesting that these pathways exhibit redundancy. We have previously demonstrated sex differences in the expression of Gas and Gaq. We have observed that female mice and humans display significantly higher levels of mRNA and protein for the G protein, Gaq. We have also observed that estrogens induce expression of Gaq mRNA and protein in female mice. In addition, preliminary studies in mice demonstrate that both ACTH (adrenocorticotropic hormone or corticotropin) and CRH (corticotropin-releasing hormone) induce Gaq in immune cells and adrenal tissue in a sex restricted fashion, i.e. females only.
ACTH and CRH are the two major hormones controlling adrenal function. Adrenal function can be tested using a standard 1mcg synthetic ACTH stimulation test and measuring the production of cortisol. We have observed that females exhibit a trend toward increased responsiveness to ACTH stimulation than males. We speculate that sex differences in cortisol responsiveness to ACTH exist, and that these differences will correlate with sex differences in the expression or induction of the G proteins, Gaq or Gas.
We propose to determine whether healthy female subjects undergoing low-dose ACTH stimulation exhibit altered levels of Gaq or Gas mRNA and protein and cortisol levels compared with male subjects undergoing the same provocative testing. This study may have implications for the interpretation of provocative ACTH testing.
- Conditions
- Adrenal Sufficiency
- Keywords
- Adrenal sufficiency, Low-dose ACTH stimulation, G proteins
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startJul 2005
- Primary completionApr 2013
- Study completionApr 2013
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 Adrenal SufficiencyStudies 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
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Mercy Hospital Kansas City
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jill D Jacobson, MD, Study director, Children's Mercy Hospital Kansas CityKelly J Seiler, MD, Principal investigator, Children's Mercy Hospital Kansas CityWayne V Moore, MD, PhD, Study chair, Children's Mercy Hospital Kansas City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00196001
- Sponsor's protocol ID
- 01.4204
- Status last verified
- Jan 2021
- First submitted
- 12 Sep 2005
- Last updated
- 13 Jan 2021
- Results posted
- No
Publications
Morton TL, Ansari MA, Jacobson JD. Gender differences and hormonal modulation of G proteins Gaq/11 expression in lymphoid organs. Neuroendocrinology 2003;78:147-153. Clark PM, Neylon I, Raggatt PR, Sheppard MC, Stewart PM. Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamic-pituitary disorders. Clin Endocrinol 1998;49:287-292. Dickstein G, Shechner C, Nicholson WE, Rosner I, Shen-Orr, Adawi F, et al. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab 1991;72:773-778. Tordjman K, Jaffe A, Grazas N, Apter C, Stern N. The role of the low dose (1 mcg) adrenocorticotropin test in the evaluation of patients with pituitary disease. J Clin Endocrinol Metab 1995;80:1301-1305. Thaler LM, Blevins LS. The low dose (1-mcg) adrenocorticotropin stimulation test in the evaluation of patients with suspected central adrenal insufficiency. J Clin Endocrinol Metab 1998;83:2726-2729. Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med 2003;139:194-204. Product Information: Acthar(R), corticotropin. Armour Pharmaceutical, Blue Bell, PA, 1990. Jacobson JD, Ansari MA, Kinealy M, Muthukrishnan V. Gender-specific exacerbation of murine lupus by gonadotropin-releasing hormone: potential role of Gaq/11. Endocrinology 1999;140:3429-3437. Chomczynski P. A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 1993;15(3):532-4, 536-7.
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- G Protein Expression in Response to ACTH Stimulation Testing
- ClinicalTrials.gov ID
- NCT00196001
- Acronym / sponsor ID
- 01.4204
- Conditions
- Adrenal Sufficiency
- Keywords
- Adrenal sufficiency, Low-dose ACTH stimulation, G proteins
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Children's Mercy Hospital Kansas CityUniversity, hospital or other
- Study start
- Jul 2005 (actual)
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 20 Sep 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.
Males and females may exhibit different responses to testing of adrenal function. The hormones responsible for controlling adrenal function are ACTH (adrenocorticotropic hormone or corticotropin) and CRH (corticotropin-releasing hormone). Adrenal function is tested with an ACTH stimulation test. ACTH stimulates the adrenal glands to produce cortisol. Cortisol levels are measured, and a certain peak level indicates normal adrenal gland function. Females may produce more cortisol in response to ACTH testing than males. This difference may be due to certain proteins, called G proteins. The hormones controlling adrenal function, ACTH and CRH, work through G proteins. Females may have more G proteins than males allowing for the increased cortisol response to ACTH stimulation.
The investigators speculate that:
- There may be differences in adrenal responsiveness to ACTH stimulation testing between healthy males and females.
- ACTH and CRH induce their own function.
- Sex differences in adrenal responsiveness to ACTH stimulation testing may be related to sex differences in G protein expression.
In this study, cortisol, a hormone produced by the adrenal glands, will be measured before and after the administration of ACTH.
This study will also measure G proteins. G proteins are found in the white blood cells. White blood cells from females may have more active G proteins than white blood cells from males. Sex differences may be augmented after exposure to ACTH.
Detailed description
Many nonsteroidal hormones work through G protein signal transducers. These heterotrimeric signal transducers couple cell surface receptors to intracellular pathways, thus conveying biologic effects. Most hormones that work via the stimulatory G protein, Gas, also exert actions through a homologous stimulatory G protein, Gaq, suggesting that these pathways exhibit redundancy. We have previously demonstrated sex differences in the expression of Gas and Gaq. We have observed that female mice and humans display significantly higher levels of mRNA and protein for the G protein, Gaq. We have also observed that estrogens induce expression of Gaq mRNA and protein in female mice. In addition, preliminary studies in mice demonstrate that both ACTH (adrenocorticotropic hormone or corticotropin) and CRH (corticotropin-releasing hormone) induce Gaq in immune cells and adrenal tissue in a sex restricted fashion, i.e. females only.
ACTH and CRH are the two major hormones controlling adrenal function. Adrenal function can be tested using a standard 1mcg synthetic ACTH stimulation test and measuring the production of cortisol. We have observed that females exhibit a trend toward increased responsiveness to ACTH stimulation than males. We speculate that sex differences in cortisol responsiveness to ACTH exist, and that these differences will correlate with sex differences in the expression or induction of the G proteins, Gaq or Gas.
We propose to determine whether healthy female subjects undergoing low-dose ACTH stimulation exhibit altered levels of Gaq or Gas mRNA and protein and cortisol levels compared with male subjects undergoing the same provocative testing. This study may have implications for the interpretation of provocative ACTH testing.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 6 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- Healthy male and female subjects (ages 6-34)
Key inclusion criteria (1 listed)
- Healthy males and females aged 6-60
Key exclusion criteria (5 listed)
- Known medical condition
- Use of inhaled, topical, or oral steroids
- Use of oral contraceptive pills or hormone replacement
- Menopause
- Pregnancy
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
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 13 Jan 2021.
- BackgroundMorton TL, Ansari MA, Jacobson JD. Gender differences and hormonal modulation of G proteins Gaq/11 expression in lymphoid organs. Neuroendocrinology 2003;78:147-153. Clark PM, Neylon I, Raggatt PR, Sheppard MC, Stewart PM. Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamic-pituitary disorders. Clin Endocrinol 1998;49:287-292. Dickstein G, Shechner C, Nicholson WE, Rosner I, Shen-Orr, Adawi F, et al. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab 1991;72:773-778. Tordjman K, Jaffe A, Grazas N, Apter C, Stern N. The role of the low dose (1 mcg) adrenocorticotropin test in the evaluation of patients with pituitary disease. J Clin Endocrinol Metab 1995;80:1301-1305. Thaler LM, Blevins LS. The low dose (1-mcg) adrenocorticotropin stimulation test in the evaluation of patients with suspected central adrenal insufficiency. J Clin Endocrinol Metab 1998;83:2726-2729. Dorin RI, Qualls CR, Crapo LM. Diagnosis of adrenal insufficiency. Ann Intern Med 2003;139:194-204. Product Information: Acthar(R), corticotropin. Armour Pharmaceutical, Blue Bell, PA, 1990. Jacobson JD, Ansari MA, Kinealy M, Muthukrishnan V. Gender-specific exacerbation of murine lupus by gonadotropin-releasing hormone: potential role of Gaq/11. Endocrinology 1999;140:3429-3437. Chomczynski P. A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques 1993;15(3):532-4, 536-7.
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.
Jill D Jacobson, MD study director
Children's Mercy Hospital Kansas City
Kelly J Seiler, MD principal investigator
Children's Mercy Hospital Kansas City
Wayne V Moore, MD, PhD study chair
Children's Mercy Hospital Kansas City
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 Adrenal Sufficiency, run by Children's Mercy Hospital Kansas City 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 1 inclusion and 5 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 13 Jan 2021. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00196001, 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 13 Jan 2021.