Clinical trial NCT02243852: Effects of Growth Hormone (GH) Deficiency and Growth Hormone Replacement on Serum Fibroblast Growth Factor 21 (FGF21)
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 type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Growth Hormone Deficiency
Keywords: Growth Hormone Deficiency (GHD)
Growth Hormone Replacement Therapy
Fibroblast Growth Factor 21 (FGF21)
Visceral Fat
Subcutaneous Fat
Lead sponsor: University of Liverpool
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2014-09-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Secondary care clinic University advertisement

Brief 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.

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 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.

Primary outcomes:
measure: FGF21
timeFrame: 6-months
Secondary outcomes:
measure: Visceral and subcutaneous fat
timeFrame: 6-months
Other outcomes:
Locations:
city: Liverpool
country: United Kingdom
facility: MARIARC
state: Merseyside
city: Liverpool
country: United Kingdom
facility: University Hospital Aintree
state: Merseyside
Study officials:
affiliation: University of Liverpool
name: Daniel J Cuthbertson, PhD
role: PRINCIPAL_INVESTIGATOR
References: