Cushing SyndromeTheHOURSNCT03343470
The Circadian Rhythm in CusHing SyndrOme in Active Phase and dUring RemiSsion (TheHOURS)
An observational study of Cushing Syndrome, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
This is an observational, open, prospective multi-centre study designed to evaluate melatonin and cortisol circadian rhythm, immunological profile and anthropometric parameters in Cushing Syndrome patients during active Remission state. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cushing Syndrome
- How many people
- 15 participants
- Where
- 1 siteItaly
- Study dates
- 8 Nov 2017to 30 Dec 2023
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Cushing Syndrome patients in active phase and during remission at 3 and 6 months.
Who may be able to join
- Cushing Syndrome during active phase
Who cannot join
- Malignancy
- Alcoholism or drug addiction
- Psychiatric disorders
- Clinical or laboratory signs of significant cardiovascular, hepatobiliary disease
- Clinically significant renal dysfunction
- Pregnancy
- Any medication with agents which could interfere with glucocorticoid kinetics and melatonin secretion
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Department of Experimental Medicine
Rome, 00161
Andrea M Isidori, MD, PhD, +390649970540, andrea.isidori@uniroma1.it
About this study
Official title: The Observational Prospective Multicentric Study on Melatonin and Cortisol Circadian Rhythm in CusHing SyndrOme Patients in Active Phase and dUring RemiSsion.
This is an observational, open, prospective multi-centre study designed to evaluate melatonin and cortisol circadian rhythm, immunological profile and anthropometric parameters in Cushing Syndrome patients during active Remission state.
Read the detailed description
Cushing Syndrome is a severe condition caused by prolonged exposure to high levels of glucocorticoids.
This is a disease with high morbidity and mortality due to metabolic, cardiovascular, coagulative, psychiatric complications of hypercortisolism.
The loss of circadian secretion of cortisol is one of the most sensitive and specific diagnostic features of Cushing's Syndrome that normalizes during remission. The evaluation of the circadian rhythm of cortisol is one of the diagnostic tests recommended by the guidelines to evaluate the state of the disease's activity.
Studies in literature have shown several correlations between states of hypercortisolism and circadian secretion of melatonin, displaying reduced melatonin secretion throughout the day and the suppression of circadian rhythm of cortisol. However, the dynamics of the normalization of melatonin circadian rhythm during remission from Cushing syndrome are unclear.
Therefore, the aim of our study is to evaluate the changes in circadian secretion of melatonin in Cushing's syndrome during active disease and during remission (3 and 6 months), according to the rational scientific influence of endogenous hypercortisolism on the function of the pineal gland. In addition, the changes in circadian secretion of cortisol, of mononuclear cells of the blood (PBMC) and of anthropometric-metabolic parameters, will be analyzed.
- Conditions
- Cushing Syndrome
- Keywords
- Cushing Syndrome, Adrenal Insufficiency, Peripheral blood mononuclear cells, Melatonin, Cortisol, Immunological profile, Cushing Disease
- Medical subject headings
- Cushing Syndrome, Adrenal Insufficiency, Pituitary ACTH Hypersecretion
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 |
|---|---|---|
| Cushing Syndrome (active phase) | Patients displaying biochemical and clinical features of active Cushing's syndrome | |
| Cushing Syndrome (during remission) | Patients at 3-6 months from remission with cortisol levels in the normal range |
What is being measured
The primary outcome is the main question the study is designed to answer.
change from baseline in measurement of melatonin secretion at 3 and 6 months
single outcome measurement of melatonin secretion
Measured: 0, +3 months, +6 months
Secondary outcomes (3)
Evaluation of immunological profile at baseline, 3 and 6 months
composite outcome measure consisting of simultaneous measurement of: PBMC profiling with flow cytometry, Full count blood cell
Measured: 0, +3 months, +6 months
Evaluation of cortisol circadian rhythm
single outcome measure of circadian cortisol secretion
Measured: 0, +3 months, +6 months
Change from baseline in measurement of anthropometric-metabolic parameters at 3 and 6 months
composite outcome measure consisting of simultaneous measurement of:body weight (kg), waist circumference (cm), blood pressure and pulse
Measured: 0, +3 months, +6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start8 Nov 2017
- Primary completion30 Dec 2023 (estimated)
- Study completion30 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cushing SyndromeStudies of the same condition, open and under way.
- More trials run by University of Roma La SapienzaThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Collaborators
- Federico II University, University of Palermo, University of Florence, Ospedali Riuniti Ancona, University of Padova
- Responsible party
- Principal investigator, Andrea M. Isidori, University of Roma La Sapienza
- Investigators
- Andrea M Isidori, MD, PhD, Principal investigator, Dept. Experimental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03343470
- Sponsor's protocol ID
- Adrenal_2
- Acronym
- TheHOURS
- Status last verified
- Nov 2022
- First submitted
- 10 Nov 2017
- Last updated
- 23 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Tomova A, Kumanov P, Robeva R, Manchev S, Konakchieva R. Melatonin secretion and non-specific immune responses are differentially expressed in corticotropin-dependent and corticotropin-independent Cushing's syndrome. Med Sci Monit. 2008 Jun;14(6):CR327-332.
PubMed 18509277Pivonello R, De Leo M, Cozzolino A, Colao A. The Treatment of Cushing's Disease. Endocr Rev. 2015 Aug;36(4):385-486. doi: 10.1210/er.2013-1048. Epub 2015 Jun 11.
PubMed 26067718Piovesan A, Terzolo M, Borretta G, Torta M, Buniva T, Osella G, Paccotti P, Angeli A. Circadian profile of serum melatonin in Cushing's disease and acromegaly. Chronobiol Int. 1990;7(3):259-61. doi: 10.3109/07420529009056984.
PubMed 2268888Fevre-Montange M, Tourniaire J, Estour B, Bajard L. 24 hour melatonin secretory pattern in Cushing's syndrome. Clin Endocrinol (Oxf). 1983 Aug;19(2):175-81. doi: 10.1111/j.1365-2265.1983.tb02979.x.
PubMed 6684004Angeli A, Gatti G, Sartori ML, Masera RG. Chronobiological aspects of the neuroendocrine-immune network. Regulation of human natural killer (NK) cell activity as a model. Chronobiologia. 1992 Jul-Dec;19(3-4):93-110. No abstract available.
PubMed 1478121
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Observational Prospective Multicentric Study on Melatonin and Cortisol Circadian Rhythm in CusHing SyndrOme Patients in Active Phase and dUring RemiSsion.
- ClinicalTrials.gov ID
- NCT03343470
- Acronym / sponsor ID
- TheHOURS / Adrenal_2
- Conditions
- Cushing Syndrome
- Keywords
- Cushing Syndrome, Adrenal Insufficiency, Peripheral blood mononuclear cells, Melatonin, Cortisol, Immunological profile, Cushing Disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Collaborators
- Federico II University, University of Palermo, University of Florence, Ospedali Riuniti Ancona, University of Padova
- Study start
- 8 Nov 2017 (actual)
- Primary completion
- 30 Dec 2023 (estimated)
- Study completion
- 30 Dec 2023 (estimated)
- First posted
- 17 Nov 2017 (actual)
- 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 is an observational, open, prospective multi-centre study designed to evaluate melatonin and cortisol circadian rhythm, immunological profile and anthropometric parameters in Cushing Syndrome patients during active Remission state.
Detailed description
Cushing Syndrome is a severe condition caused by prolonged exposure to high levels of glucocorticoids.
This is a disease with high morbidity and mortality due to metabolic, cardiovascular, coagulative, psychiatric complications of hypercortisolism.
The loss of circadian secretion of cortisol is one of the most sensitive and specific diagnostic features of Cushing's Syndrome that normalizes during remission. The evaluation of the circadian rhythm of cortisol is one of the diagnostic tests recommended by the guidelines to evaluate the state of the disease's activity.
Studies in literature have shown several correlations between states of hypercortisolism and circadian secretion of melatonin, displaying reduced melatonin secretion throughout the day and the suppression of circadian rhythm of cortisol. However, the dynamics of the normalization of melatonin circadian rhythm during remission from Cushing syndrome are unclear.
Therefore, the aim of our study is to evaluate the changes in circadian secretion of melatonin in Cushing's syndrome during active disease and during remission (3 and 6 months), according to the rational scientific influence of endogenous hypercortisolism on the function of the pineal gland. In addition, the changes in circadian secretion of cortisol, of mononuclear cells of the blood (PBMC) and of anthropometric-metabolic parameters, will be analyzed.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cushing Syndrome (active phase) | – | –Patients displaying biochemical and clinical features of active Cushing's syndrome |
| Cushing Syndrome (during remission) | – | –Patients at 3-6 months from remission with cortisol levels in the normal range |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Cushing Syndrome patients in active phase and during remission at 3 and 6 months.
Key inclusion criteria (1 listed)
- Cushing Syndrome during active phase
Key exclusion criteria (7 listed)
- Malignancy
- Alcoholism or drug addiction
- Psychiatric disorders
- Clinical or laboratory signs of significant cardiovascular, hepatobiliary disease
- Clinically significant renal dysfunction
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
change from baseline in measurement of melatonin secretion at 3 and 6 months
Time frame: 0, +3 months, +6 months
single outcome measurement of melatonin secretion
3 secondary outcomes
Evaluation of immunological profile at baseline, 3 and 6 months
Time frame: 0, +3 months, +6 months
Evaluation of cortisol circadian rhythm
Time frame: 0, +3 months, +6 months
Change from baseline in measurement of anthropometric-metabolic parameters at 3 and 6 months
Time frame: 0, +3 months, +6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2022.
- Results publication: PubMed 18509277Tomova A, Kumanov P, Robeva R, Manchev S, Konakchieva R. Melatonin secretion and non-specific immune responses are differentially expressed in corticotropin-dependent and corticotropin-independent Cushing's syndrome. Med Sci Monit. 2008 Jun;14(6):CR327-332.
- Results publication: PubMed 26067718Pivonello R, De Leo M, Cozzolino A, Colao A. The Treatment of Cushing's Disease. Endocr Rev. 2015 Aug;36(4):385-486. doi: 10.1210/er.2013-1048. Epub 2015 Jun 11.
- Results publication: PubMed 2268888Piovesan A, Terzolo M, Borretta G, Torta M, Buniva T, Osella G, Paccotti P, Angeli A. Circadian profile of serum melatonin in Cushing's disease and acromegaly. Chronobiol Int. 1990;7(3):259-61. doi: 10.3109/07420529009056984.
- Results publication: PubMed 6684004Fevre-Montange M, Tourniaire J, Estour B, Bajard L. 24 hour melatonin secretory pattern in Cushing's syndrome. Clin Endocrinol (Oxf). 1983 Aug;19(2):175-81. doi: 10.1111/j.1365-2265.1983.tb02979.x.
- Results publication: PubMed 1478121Angeli A, Gatti G, Sartori ML, Masera RG. Chronobiological aspects of the neuroendocrine-immune network. Regulation of human natural killer (NK) cell activity as a model. Chronobiologia. 1992 Jul-Dec;19(3-4):93-110. No abstract available.
Related trials for Cushing Syndrome
Not yet recruitingPhase 2
Osilodrostat for Glycemic Control in Mild Autonomous Cortisol Secretion (MACS) With Difficult-To-Control Type 2 Diabetes - A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study
Mild Autonomous Cortisol Secretion (MACS), Diabetes Mellitus (Type 2)
Not yet recruitingObservational study
Automated Capture of Core Data for Rare Diseases and Glucocorticoid Complications: Biomarkers and Patient-Reported Outcomes
Cushing s Syndrome, Glucocorticoid Effect
RecruitingObservational study
Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
Cushing s Syndrome, Cushing Disease
Active, not recruitingPhase 2
Extension Study to Evaluate the Safety of Long-Term Use of Relacorilant in Patients With Cushing Syndrome
Cushing Syndrome
RecruitingPhase 1/2
Diagnostic Value of CXCR4-targeted PET/CT in ACTH-dependent and Independent Cushing's Syndrome
Cushing s Syndrome
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.
Andrea M Isidori, MD, PhD principal investigator
Dept. Experimental Medicine
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 Cushing Syndrome, run by University of Roma La Sapienza at 1 site in Italy.
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 7 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: status not confirmed, as of the sponsor's last update on 23 Nov 2022. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrea M Isidori, MD, PhD (+390649970540, andrea.isidori@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change from baseline in measurement of melatonin secretion at 3 and 6 months (time frame: 0, +3 months, +6 months). 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 NCT03343470, which also lists 5 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 23 Nov 2022.