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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02360046
Other study ID # 211/14
Secondary ID 2014 DR 4137
Status Terminated
Phase N/A
First received
Last updated
Start date January 2015
Est. completion date December 2016

Study information

Verified date October 2018
Source University Hospital Inselspital, Berne
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 insufficiency.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 30
Est. completion date December 2016
Est. primary completion date December 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Written informed consent

- Male and female patients

- Corticotropic pituitary insufficiency

- Capable to exercise during 120 minutes on a bicycle

- Normal ECG during ergometry

Exclusion Criteria

- 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

- 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

Study Design


Intervention

Drug:
Hydrocortisone
Established Hydrocortisone replacement therapy plus Hydrocortisone (10mg/day)
Placebo
Established Hydrocortisone replacement therapy plus Placebo (0mg Hydrocortisone)

Locations

Country Name City State
Switzerland Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Berne Berne

Sponsors (1)

Lead Sponsor Collaborator
University Hospital Inselspital, Berne

Country where clinical trial is conducted

Switzerland, 

References & Publications (2)

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. — View Citation

Danilowicz 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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Change from baseline in flexibility of Intramyocellular Lipids (IMCL) Measured in mmol/L Measured in mmol/L 3 months
Primary Change from baseline in flexibility of Intrahepatocellular Lipids (IHCL) Measured in mmol/L Measured in mmol/L 3 months
Secondary Free Fatty Acids (FFA) availability during exercise before and after additional hydrocortisone/placebo Measured in mmol/L Measured in mmol/L At baseline, 3 months
Secondary 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 At baseline, 3 months
Secondary 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 At baseline, 3 months
Secondary Effect of exercise on insulin at baseline At baseline
Secondary Effect of exercise on insulin at 3 months 3 months
Secondary Effect of exercise on catecholamines at baseline At baseline
Secondary Effect of exercise on catecholamines at 3 months 3 months
Secondary Effect of exercise on growth hormone at baseline At baseline
Secondary Effect of exercise on growth hormone at 3 months 3 months
Secondary Effect of exercise on cortisol at baseline At baseline
Secondary Effect of exercise on cortisol at 3 months 3 months
Secondary Effect of exercise on lactate at baseline At baseline
Secondary Effect of exercise on lactate at 3 months 3 months
Secondary Effect of exercise on glucose at baseline At baseline
Secondary Effect of exercise on glucose at 3 months 3 months
Secondary Effect of exercise on inflammatory markers at baseline At baseline
Secondary Effect of exercise on inflammatory markers at 3 months 3 months
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