Lipolytic Effects of GH in Hypopituitary Patients in Vivo

March 25, 2020 updated by: University of Aarhus

Lipolytic Effects of GH in Hypopituitary Patients in Vivo: Molecular Mechanisms and Temporal Patterns.

Growth hormone (GH) is essential for longitudinal bone growth and somatic development. These protein anabolic effects require sufficient nutritional supply. During fasting and caloric restriction GH predominantly promotes fat metabolism.

GH counteracts the effect of insulin in many tissues, of which insulin-stimulated glucose uptake in skeletal muscle has been most extensively studied. Substrate competition between elevated free fatty acids and glucose is suggested as a mechanism, and this hypothesis can be tested mechanistically by means of acipimox, which is a nicotinic acid that suppresses the fat metabolizing effects of GH.

The hypothesis is, that the suppressive effect of GH on insulin-stimulated glucose uptake in skeletal muscle is obviated by acipimox-induced inhibition of fat metabolism.

In order to investigate this, eight adult hypopituitary patients with documented GH-deficiency will be studied in the presence and absence of GH and acipimox, respectively, and biopsies from skeletal muscle and subcutaneous adipose tissue will be analyzed.

Knowledge of the effects of growth hormone and fat metabolism can in shot-sight as well as in long-sight have great importance for the understanding of growth disorders from overweight and type 2 diabetes to malnutrition and eating disorders.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus, Denmark, 8000
        • University Hospital of Aarhus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • hypopituitary patients with documented GH-deficiency

Exclusion Criteria:

  • other significant disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Acipimox/GH substitution
Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Continue GH substitution as usually.
Drug: Acipimox
Acipimox is administered 4 times previous to and during the investigation day. Acipimox is used to suppress the lipolytic effect of GH.
Other Names:
  • Olbetam
Drug: GH substitution
GH substitution as usually
Active Comparator: Acipimox/GH pause
Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Pause GH substitution to days prior to the study day.
Drug: Acipimox
Acipimox is administered 4 times previous to and during the investigation day. Acipimox is used to suppress the lipolytic effect of GH.
Other Names:
  • Olbetam
Other: GH pause
GH substitution pause two days prior to the experimental day
Placebo Comparator: Placebo/GH substitution
Drug: Placebo tablets Continue GH substitution as usually.
Drug: GH substitution
GH substitution as usually
Drug: Placebo
Placebo is administered 4 times previous to and during the investigation day.
Placebo Comparator: Placebo/GH pause
Drug: Placebo tablets Pause GH substitution to days prior to the study day.
Other: GH pause
GH substitution pause two days prior to the experimental day
Drug: Placebo
Placebo is administered 4 times previous to and during the investigation day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Lipolytic activity measured as area under the curve (AUC) for FFA (free fatty acid) before and during clamp-conditions.
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
GH signaling proteins and gene targets in adipose and skeletal muscle tissues measured by western blotting and qPCR
Time Frame: 1,5 years
1,5 years
Insulin sensitivity as measured by M value and GIR (glucose infusion rate)
Time Frame: 6 months
6 months
Substrate metabolism as measured by indirect calorimetry, tritiated glucose and circulating hormones and metabolites
Time Frame: 1 year
1 year
PDH (pyruvate dehydrogenase) activity in skeletal muscle measured by an PDH activity assay
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Investigators

  • Principal Investigator: Jens Otto L Jørgensen, Professor, University Hospital of Aarhus

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 10, 2016

Primary Completion (Actual)

December 22, 2016

Study Completion (Actual)

December 22, 2016

Study Registration Dates

First Submitted

May 18, 2016

First Submitted That Met QC Criteria

May 20, 2016

First Posted (Estimate)

May 25, 2016

Study Record Updates

Last Update Posted (Actual)

March 26, 2020

Last Update Submitted That Met QC Criteria

March 25, 2020

Last Verified

October 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GHD01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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