HypopituitarismHydrocortNCT02360046
The Influence of Different Hydrocortisone Replacement Doses on the Partitioning and Flexibility of Ectopic Lipids in Patients With Corticotropic Hypopituitarism
A study testing Hydrocortisone in people with Hypopituitarism and Hydrocortisone, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
This study aims at assessing the effect of today's standard of hydrocortisone dosage versus previous hydrocortisone dosage on flexibility and partitioning of ectopic lipid depots (IMCL and IHCL) after a standardised fat load followed by a short-term aerobic exercise in patients with corticotropic pituitary… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypopituitarism, Hydrocortisone, Lipids
- What is being tested?
- Hydrocortisone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jan 2015to Dec 2016
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- Male and female patients
- Corticotropic pituitary insufficiency
- Capable to exercise during 120 minutes on a bicycle
- Normal ECG during ergometry
Who cannot join
- Concomitant medication with NSAID, anticoagulants, digoxin, salbutamol, anticonvulsants, cholinesterase inhibitor, pancuronium
- Abnormal liver, renal or thyroid function, heart failure
- Hemophilia
- Diabetes mellitus
- Severe dyslipidemia
- Active neoplasia
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- Women who are pregnant or breast feeding
- Intention to become pregnant during the course of the study
- Lack of safe contraception
- Known or suspected non-compliance
- Drug or alcohol abuse
- Inability to follow the procedures of the study
- Participation in another study with investigational drug within the 30 days preceding and during the study
- Previous enrolment into current study
- Enrolment of the investigator, his/her family members, employees and other dependent persons
- Inability to exercise
- Contraindications to exposure to a 3 T magnetic field
- Major depression, psychosis, claustrophobia
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Berne
Bern, 3010
About this study
Official title: The Influence of Different Hydrocortisone Replacement Doses on the Partitioning and Flexibility of Ectopic Lipids (Intrahepatocellular IHCL and Intramyocellular IMCL) in Patients With Corticotropic Hypopituitarism, a Randomised Placebo-controlled Double-blind Trial
This study aims at assessing the effect of today's standard of hydrocortisone dosage versus previous hydrocortisone dosage on flexibility and partitioning of ectopic lipid depots (IMCL and IHCL) after a standardised fat load followed by a short-term aerobic exercise in patients with corticotropic pituitary insufficiency.
Read the detailed description
Background
The investigators and others have shown that long-term hydrocortisone replacement therapy at higher doses of hydrocortisone replacement therapy at higher doses of hydrocortisone replacement (as previously recommended) is associated with higher mortality. The pathophysiology for the association of hydrocortisone-replacement dose and mortality remains unclear. A possible underlying mechanism is nonalcoholic fatty liver disease which is more prevalent in patients with hypopituitarism. Patients with non-alcoholic fatty liver disease are at a higher risk for overall-mortality.
It remains to be established whether the insulin resistance, associated with increased intrahepatocellular lipids and increased intramusculoskeletal lipids, is implicated in the pathophysiology of these epidemiological findings.
Interestingly, it has been shown that a reduction of hydrocortisone replacement dose from 20-30mg/d to 10-15mg/d resulted in a loss of body fat and a significant decrease of plasma total cholesterol and triglyceride concentration. The effect of IMCL and IHCL is so far unknown.
Patients with hypopituitarism with hydrocortisone replacement therapy provide a unique disease model to study the short-term effects of previously recommended dose (higher dose) of hydrocortisone versus lower dose of HC replacement therapy on ectopic lipids (IMCL; IHCL) lipids, as well as on subcutaneous and visceral fat mass and on parameters of insulin resistance. Combining MRI and MR-spectroscopy techniques, different fat mass (subcutaneous and visceral) and ectopic lipids can be repeatedly and non-invasively assessed.
Objective
To investigate the impact of today's standard of hydrocortisone dosage (lower) versus previous (higher) hydrocortisone dosage on flexibility and partitioning of ectopic lipid depots after a standardised fat load followed by a short-term aerobic exercise in patients with corticotropic pituitary insufficiency.
Methods
Ectopic lipids are measured by MR-spectroscopy, separate assessment of visceral and subcutaneous fat mass will be performed by MR-imaging, standardized exercise capacity test using spiroergometry. Short-time exercise consists of 2h aerobic cycling at 50% VO2max. Laboratory analysis include lipid profile, free fatty acids, HOMA-Index, hormones.
- Being tested
- Hydrocortisone, Placebo
- Medical subject headings
- Hypopituitarism, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrocortisoneDrug
Established Hydrocortisone replacement therapy plus Hydrocortisone (10mg/day)
PlaceboDrug
Established Hydrocortisone replacement therapy plus Placebo (0mg Hydrocortisone)
| Study group | Role | What they receive |
|---|---|---|
| Higher hydrocortisone dose | Other | Established hydrocortisone replacement therapy plus 10mg of hydrocortisone Receives: Drug: Hydrocortisone |
| Lower hydrocortisone dose | Other | Established hydrocortisone replacement therapy plus placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in flexibility of Intramyocellular Lipids (IMCL) Measured in mmol/L
Measured in mmol/L
Measured: 3 months
Change from baseline in flexibility of Intrahepatocellular Lipids (IHCL) Measured in mmol/L
Measured in mmol/L
Measured: 3 months
Secondary outcomes (17)
Free Fatty Acids (FFA) availability during exercise before and after additional hydrocortisone/placebo Measured in mmol/L
Measured in mmol/L
Measured: At baseline, 3 months
Flexibility of ectopic fat stores, defined as difference between intramyocellular/intrahepatocellular lipid concentration before and after exercise, and their possible relation to insulin sensitivity before and after additional hydrocortisone/placebo
Measured: At baseline, 3 months
Free Fatty Acids (FFA) availability during exercise and the possible relation to insulin sensitivity before and after additional hydrocortisone/placebo Measured in mmol/L
Measured in mmol/L
Measured: At baseline, 3 months
Effect of exercise on insulin at baseline
Measured: At baseline
Effect of exercise on insulin at 3 months
Measured: 3 months
Effect of exercise on catecholamines at baseline
Measured: At baseline
Effect of exercise on catecholamines at 3 months
Measured: 3 months
Effect of exercise on growth hormone at baseline
Measured: At baseline
Effect of exercise on growth hormone at 3 months
Measured: 3 months
Effect of exercise on cortisol at baseline
Measured: At baseline
Effect of exercise on cortisol at 3 months
Measured: 3 months
Effect of exercise on lactate at baseline
Measured: At baseline
Effect of exercise on lactate at 3 months
Measured: 3 months
Effect of exercise on glucose at baseline
Measured: At baseline
Effect of exercise on glucose at 3 months
Measured: 3 months
Effect of exercise on inflammatory markers at baseline
Measured: At baseline
Effect of exercise on inflammatory markers at 3 months
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2015 (estimated)
- Study startJan 2015
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypopituitarismStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emanuel Christ, MD, PhD, Principal investigator, Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital BernChris Boesch, MD, PhD, Principal investigator, AMSM; Division of Radiology, University Hopsital of Bern, Inselspital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02360046
- Sponsor's protocol ID
- 211/14
- Other IDs
- 2014 DR 4137
- Acronym
- Hydrocort
- Status last verified
- Oct 2018
- First submitted
- 16 Jan 2015
- Last updated
- 9 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Boesch C, Slotboom J, Hoppeler H, Kreis R. In vivo determination of intra-myocellular lipids in human muscle by means of localized 1H-MR-spectroscopy. Magn Reson Med. 1997 Apr;37(4):484-93. doi: 10.1002/mrm.1910370403.
PubMed 9094069Danilowicz K, Bruno OD, Manavela M, Gomez RM, Barkan A. Correction of cortisol overreplacement ameliorates morbidities in patients with hypopituitarism: a pilot study. Pituitary. 2008;11(3):279-85. doi: 10.1007/s11102-008-0126-2.
PubMed 18459045
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Different Hydrocortisone Replacement Doses on the Partitioning and Flexibility of Ectopic Lipids (Intrahepatocellular IHCL and Intramyocellular IMCL) in Patients With Corticotropic Hypopituitarism, a Randomised Placebo-controlled Double-blind Trial
- ClinicalTrials.gov ID
- NCT02360046
- Acronym / sponsor ID
- Hydrocort / 211/14
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 10 Feb 2015 (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 aims at assessing the effect of today's standard of hydrocortisone dosage versus previous hydrocortisone dosage on flexibility and partitioning of ectopic lipid depots (IMCL and IHCL) after a standardised fat load followed by a short-term aerobic exercise in patients with corticotropic pituitary insufficiency.
Detailed description
Background
The investigators and others have shown that long-term hydrocortisone replacement therapy at higher doses of hydrocortisone replacement therapy at higher doses of hydrocortisone replacement (as previously recommended) is associated with higher mortality. The pathophysiology for the association of hydrocortisone-replacement dose and mortality remains unclear. A possible underlying mechanism is nonalcoholic fatty liver disease which is more prevalent in patients with hypopituitarism. Patients with non-alcoholic fatty liver disease are at a higher risk for overall-mortality.
It remains to be established whether the insulin resistance, associated with increased intrahepatocellular lipids and increased intramusculoskeletal lipids, is implicated in the pathophysiology of these epidemiological findings.
Interestingly, it has been shown that a reduction of hydrocortisone replacement dose from 20-30mg/d to 10-15mg/d resulted in a loss of body fat and a significant decrease of plasma total cholesterol and triglyceride concentration. The effect of IMCL and IHCL is so far unknown.
Patients with hypopituitarism with hydrocortisone replacement therapy provide a unique disease model to study the short-term effects of previously recommended dose (higher dose) of hydrocortisone versus lower dose of HC replacement therapy on ectopic lipids (IMCL; IHCL) lipids, as well as on subcutaneous and visceral fat mass and on parameters of insulin resistance. Combining MRI and MR-spectroscopy techniques, different fat mass (subcutaneous and visceral) and ectopic lipids can be repeatedly and non-invasively assessed.
Objective
To investigate the impact of today's standard of hydrocortisone dosage (lower) versus previous (higher) hydrocortisone dosage on flexibility and partitioning of ectopic lipid depots after a standardised fat load followed by a short-term aerobic exercise in patients with corticotropic pituitary insufficiency.
Methods
Ectopic lipids are measured by MR-spectroscopy, separate assessment of visceral and subcutaneous fat mass will be performed by MR-imaging, standardized exercise capacity test using spiroergometry. Short-time exercise consists of 2h aerobic cycling at 50% VO2max. Laboratory analysis include lipid profile, free fatty acids, HOMA-Index, hormones.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Higher hydrocortisone dose | Other | Drug: HydrocortisoneEstablished hydrocortisone replacement therapy plus 10mg of hydrocortisone |
| Lower hydrocortisone dose | Other | Drug: PlaceboEstablished hydrocortisone replacement therapy plus placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Written informed consent
- Male and female patients
- Corticotropic pituitary insufficiency
- Capable to exercise during 120 minutes on a bicycle
- Normal ECG during ergometry
Key exclusion criteria (18 listed)
- Concomitant medication with NSAID, anticoagulants, digoxin, salbutamol, anticonvulsants, cholinesterase inhibitor, pancuronium
- Abnormal liver, renal or thyroid function, heart failure
- Hemophilia
- Diabetes mellitus
- Severe dyslipidemia
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 |
|---|---|---|
| HydrocortisoneEstablished Hydrocortisone replacement therapy plus Hydrocortisone (10mg/day) | Drug | Higher hydrocortisone dose |
| PlaceboEstablished Hydrocortisone replacement therapy plus Placebo (0mg Hydrocortisone) | Drug | Lower hydrocortisone dose |
Primary outcome
Change from baseline in flexibility of Intramyocellular Lipids (IMCL) Measured in mmol/L
Time frame: 3 months
Measured in mmol/L
Change from baseline in flexibility of Intrahepatocellular Lipids (IHCL) Measured in mmol/L
Time frame: 3 months
Measured in mmol/L
17 secondary outcomes
Free Fatty Acids (FFA) availability during exercise before and after additional hydrocortisone/placebo Measured in mmol/L
Time frame: At baseline, 3 months
Flexibility of ectopic fat stores, defined as difference between intramyocellular/intrahepatocellular lipid concentration before and after exercise, and their possible relation to insulin sensitivity before and after additional hydrocortisone/placebo
Time frame: At baseline, 3 months
Free Fatty Acids (FFA) availability during exercise and the possible relation to insulin sensitivity before and after additional hydrocortisone/placebo Measured in mmol/L
Time frame: At baseline, 3 months
Effect of exercise on insulin at baseline
Time frame: At baseline
Effect of exercise on insulin at 3 months
Time frame: 3 months
Effect of exercise on catecholamines at baseline
Time frame: At baseline
Effect of exercise on catecholamines at 3 months
Time frame: 3 months
Effect of exercise on growth hormone at baseline
Time frame: At baseline
Effect of exercise on growth hormone at 3 months
Time frame: 3 months
Effect of exercise on cortisol at baseline
Time frame: At baseline
Effect of exercise on cortisol at 3 months
Time frame: 3 months
Effect of exercise on lactate at baseline
Time frame: At baseline
Effect of exercise on lactate at 3 months
Time frame: 3 months
Effect of exercise on glucose at baseline
Time frame: At baseline
Effect of exercise on glucose at 3 months
Time frame: 3 months
Effect of exercise on inflammatory markers at baseline
Time frame: At baseline
Effect of exercise on inflammatory markers at 3 months
Time frame: 3 months
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2018.
- Background: PubMed 9094069Boesch C, Slotboom J, Hoppeler H, Kreis R. In vivo determination of intra-myocellular lipids in human muscle by means of localized 1H-MR-spectroscopy. Magn Reson Med. 1997 Apr;37(4):484-93. doi: 10.1002/mrm.1910370403.
- Background: PubMed 18459045Danilowicz K, Bruno OD, Manavela M, Gomez RM, Barkan A. Correction of cortisol overreplacement ameliorates morbidities in patients with hypopituitarism: a pilot study. Pituitary. 2008;11(3):279-85. doi: 10.1007/s11102-008-0126-2.
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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.
Emanuel Christ, MD, PhD principal investigator
Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Bern
Chris Boesch, MD, PhD principal investigator
AMSM; Division of Radiology, University Hopsital of Bern, Inselspital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hydrocortisone in people with Hypopituitarism and Hydrocortisone, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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 5 inclusion and 18 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: stopped early, as of the sponsor's last update on 9 Oct 2018. 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 Switzerland. 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 was stopped early. Results are not available in the source record.
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?
Change from baseline in flexibility of Intramyocellular Lipids (IMCL) Measured in mmol/L (time frame: 3 months). The study lists 2 primary outcomes in all. 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 NCT02360046, which also lists 2 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 9 Oct 2018.