Leptin in hepatic lipid metabolism in humans

• Register: EUCTR
• Last refreshed on: 23 July 2018
• Main ID: EUCTR2017-003014-22-AT
• Date of registration: 29/05/2018
• Prospective Registration: Yes
• Primary sponsor: Medical University of Vienna
• Public title: Leptin in hepatic lipid metabolism in humans
• Scientific title: The role of leptin in regulating hepatic lipid metabolism in humans - Leptin and hepatic lipid metabolism
• Date of first enrolment: 25/06/2018
• Target sample size: 43
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003014-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria

Contacts

• Name: Sekretariat Endokrinologie
• Affiliation: Medical University of Vienna

• Name: Sekretariat Endokrinologie
• Affiliation: Medical University of Vienna

Key inclusion & exclusion criteria

Inclusion criteria:
+ Age between 18 – 70 years
+ Plasma trigylcerides = 700 mg/dl (aim 2 and 3 – lipodystrophic/LTX cohort; Healthy human subject cohort: < 150 mg/dl
+ male sex (healthy human subject cohort); female patients are eligible in LTX/lipodystrophic cohort
+ patients with generalized or partial lipodystrophy (based on clinical/genetic diagnosis): drug-naive patients will be preferentially recruited in case an N of 4-5 cannot be met, patients off-treatment are also recruited; no metreleptin treatment 2-3 weeks prior to the study (note that metreleptin treatment will be tapered before discontinuation to avoid triglyceride rebound in case patients are on metreleptin
+ LTX cohort: no major change (i.e. drug-class switch; dose adjustments are allowed) in immunosuppressive therapy regime in the last 4 weeks; > 6 months after LTX
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
+ overt diabetes mellitus (HbA1c = 6.5%); except for lipodystrophy patients (aim 3)
+ history of recent acute pancreatitis (< 6 months)
+ serum TGs > 700mg/dl
+ severe liver disease (LFTs 3x ULN)
+ pregnancy
+ T-Cell Lymphoma
+ Autoimmune disease
+ consummation of alcoholic beverages during the last 48 hours
+ history of polyneuropathy or gastropareses (including regular use of gabapentin and/or metoclopramide or other common drugs to treat gastropareses or neuropathy)
+ body-Mass-Index > 35 kg/m²
+ tendency towards claustrophobia
+ simultaneous participation in another active clinical study
+ allergies against soy products, eggs, peanuts (in case intralipid is infused)
+ glomerular filtration rate < 65 mL/min/1.73 m2 (calculated with the MDRD formula)
+ healthy subjects with a hepatic lipid content = 10 % water signal are excluded
+ metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation [heart pacemaker, coronary stents and heart valves (in case these devices are not compatible with a 7T MT), brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

lipodystrophy patients, patients after liver transplantation and healthy controls

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: Myalept
Product Name: Myalept
Pharmaceutical Form: Concentrate and solvent for solution for injection
INN or Proposed INN: metrelpetin
Current Sponsor code: Thalamus_V2
Other descriptive name: METRELEPTIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: Define the role of leptin action in regulating hepatic VLDL secretion, lipid content and energy metabolism in healthy human subjects

Primary end point(s): • Leptin induced changes in VLDL secretion
• Impact of vagal stimulation on VLDL secretion

Secondary Objective: Assess leptin action in denervated livers.
Assess the effects of leptin in patients with lipodystrophy.

Timepoint(s) of evaluation of this end point: at baseline and 180 minutes after s.c. injection of metreleptin or placebo

Secondary Outcome(s)

Secondary end point(s): • Changes in hepatic lipid content
• Changes in metabolism of energy rich phosphates (ATP turnover)
• Impact of hepatic denervation on VLDL secretion

Timepoint(s) of evaluation of this end point: at baseline and 180 minutes after s.c. injection of metreleptin or placebo

Secondary ID(s)

Thalamus_V3

Source(s) of Monetary Support

Medical University of Vienna