Effects of Growth Hormone (GH) Deficiency and Growth Hormone Replacement on Serum Fibroblast Growth Factor 21 (FGF21)
Information source: University of Liverpool
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Growth Hormone Deficiency
Intervention: Growth Hormone Replacement Therapy (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: University of Liverpool Official(s) and/or principal investigator(s): Daniel J Cuthbertson, PhD, Principal Investigator, Affiliation: University of Liverpool
Overall contact: Daniel J Cuthbertson, PhD, Phone: +441515295911, Email: daniel.cuthbertson@liverpool.ac.uk
Summary
This study will recruit healthy controls (who have normal GH production and growth hormone
levels) and patients identified as having GHD, who are deemed eligible for GH replacement
therapy according to NICE guidelines. The patients recruited will have been identified as
starting on GH by their referring clinicians and a decision made on their replacement
therapy prior to their potential enrollment in the study. The study, or its research team,
will have no influence on the decision as to whether a patient will start on GH, or on which
of the many GH formulations that the patients receives. The proposed study is an
observational study to determine how GH affects the plasma levels of Fibroblast growth
factor 21 (FGF21) in response to treatment; and whether the change in FGF21 mirrors the
improvement in body composition/fat deposition. FGF21 is a metabolic regulator that acts on
multiple tissues to coordinate carbohydrate and lipid metabolism and regulate energy
balance.
We hypothesize that FGF-21 is expressed and secreted from liver and skeletal muscle in
humans in response to growth hormone administration and that levels may be reduced in
patients with GHD compared with healthy controls. Furthermore, we believe that the
beneficial effects of long-term GH replacement on body composition (reduction in visceral
adipose tissue, subcutaneous adipose tissue and liver fat), on improvement in lipid profiles
and on skeletal muscle mitochondrial function involve GH-induced release of FGF21.
Clinical Details
Official title: Evaluation of the Effects of Growth Hormone (GH) Deficiency and Growth Hormone Replacement on Serum Fibroblast Growth Factor 21 (FGF21) Concentration in Patients With Growth Hormone Deficiency (GHD)
Study design: Observational Model: Case Control, Time Perspective: Prospective
Primary outcome: FGF21
Secondary outcome: Visceral and subcutaneous fat
Detailed description:
Growth hormone (GH) is involved in controlling people's general health and an
underproduction of growth hormone (growth hormone deficiency or GHD) leads to people feeling
generally unwell and having a lower feeling of well-being and quality of life scores. In
addition, the investigators, and others, have demonstrated people with GHD have reduced
muscle and bone strength and a greater storage of fat, particularly in unfavourable sites
such as in the liver and within the abdomen (visceral fat), rather than beneath the skin
(subcutaneous fat).
Treatment of GHD is achieved by administration of GH replacement therapy, given as a once
daily subcutaneous injection, which generally reverses these symptoms. Due to its high cost,
patients are only started on GH replacement depending on the impact that the GHD is having
on their quality of life. Patients must be severely affected to be eligible for replacement
therapy. Patients are screened for quality of life using a well validated, disease specific
questionnaire (AGHDA, Adult Growth hormone deficiency questionnaire) and there are specific
criteria that govern whether a patient with GHD warrants GH replacement and also whether
they continue treatment (NICE guideline: Growth hormone deficiency (adults) - human growth
hormone (TA64)).
This study will specifically determine whether the mechanism of action by which GH exerts
its beneficial effects on metabolism (within adipose tissue and skeletal muscle) involves
changes in serum FGF21 concentrations.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
All evaluations to determine eligibility into the study and for growth hormone replacement
are performed as part of routine clinical care. It should be emphasised that no research
specific screening tests will be performed. Patients deemed eligible for entry into study,
who decline to participate in the research, will still be commenced on growth hormone in
line routine clinical care.
Inclusion criteria: Patients with confirmed GH deficiency who are deemed eligible for GH
replacement as assessed by the AGHDA QOL questionnaire.
Exclusion criteria: Claustrophobia or having significant metal work is a contra-indication
to MRI scanning.
Withdrawal criteria: Patients will be withdrawn from the study if they discontinue their
growth hormone replacement therapy for any clinical reason.
Locations and Contacts
Daniel J Cuthbertson, PhD, Phone: +441515295911, Email: daniel.cuthbertson@liverpool.ac.uk
MARIARC, Liverpool, Merseyside L69 3GE, United Kingdom; Recruiting Graham J Kemp, PhD, Phone: +44-151-706-4086, Email: g.j.kemp@liv.ac.uk Graham J Kemp, PhD, Principal Investigator
University Hospital Aintree, Liverpool, Merseyside L9 7AL, United Kingdom; Recruiting Daniel J Cuthbertson, PhD, Phone: +44 151 529 5911, Email: daniel.cuthbertson@liverpool.ac.uk Daniel J Cuthbertson, PhD, Principal Investigator
Additional Information
Starting date: September 2014
Last updated: September 18, 2014
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