Effects of Growth Hormone (GH) Deficiency and Growth Hormone Replacement on Serum Fibroblast Growth Factor 21 (FGF21)

NCT02243852 | Withdrawn

• 1 other identifier: 13/NW/0075
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Growth Hormone Deficiency

Keywords

Growth Hormone Deficiency (GHD); Growth Hormone Replacement Therapy; Fibroblast Growth Factor 21 (FGF21); Visceral Fat; Subcutaneous Fat

Outcome Measures

Primary Outcomes (1)

• FGF21

  The primary outcome measure involves differences in serum FGF21 concentration between healthy controls and GHD patients, and changes in FGF21 concentration with GH replacement in patients with GHD

  6-months

Secondary Outcomes (1)

• Visceral and subcutaneous fat

  6-months

Study Arms (3)

Growth Hormone Deficiency (n=16)

16 asymptomatic GHD patients (who have confirmed GHD but who remain without GH replacement) will be compared with 16 healthy controls. Participants will be asked to undertake a single fasting blood sample and an MRI scan (whole body MRI and proton- and phosphorus-MR spectroscopy) to determine VAT, SAT and liver fat and muscle mitochondrial function. FGF21, body composition and mitochondrial function will be assessed in each of cohort to determine the correlation of FGF21 levels with VAT, SAT and liver fat.

Healthy Controls (n=16)

16 healthy controls will be compared with 16 asymptomatic GHD patients (who have confirmed GHD but who remain without GH replacement). Participants will be asked to undertake a single fasting blood sample and an MRI scan (whole body MRI and proton- and phosphorus-MR spectroscopy) to determine VAT, SAT and liver fat and muscle mitochondrial function. FGF21, body composition and mitochondrial function will be measured in all cohorts to determine the correlation of FGF21 levels with VAT, SAT and liver fat.

Growth Hormone Replacement Therapy (n=16)

GHD patients, who are eligible for GH replacement therapy as part of their routine clinical care, according to the National Institute for Clinical Excellence (NICE) recommendations, based on the biochemical deficiency and the appropriate AGHDA questionnaire score (AGHDA score\>11) will be recruited. These patients attend the Joint Endocrine clinic at University Hospital Aintree, Liverpool, and those who are about to commence growth hormone replacement will be asked to participate in this observational study. Anthropometric, biochemical including measurement of FGF21 and MR evaluation will be carried out in patients who are to be treated with GH as part of their routine clinical care immediately prior to GH therapy and after six months of replacement treatment. The type of GH and dose of treatment will be at the discretion of the treating physician. Standard doses will be used and patients will remain under the care of the supervising

Drug: Growth Hormone Replacement Therapy

Interventions

Growth Hormone Replacement Therapy DRUG

An observational study of patients who are commencing GH replacement as part of their routine NHS clinical care to assess changes in serum FGF21 concentration and determine how these relate to changes in body composition.

Growth Hormone Replacement Therapy (n=16)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Secondary care clinic University advertisement

You may not qualify if:

• Withdrawal criteria: Patients will be withdrawn from the study if they discontinue their growth hormone replacement therapy for any clinical reason.

Sponsors & Collaborators

• University of Liverpool: lead
• Pfizer: collaborator

Study Sites (2)

MARIARC

Liverpool, Merseyside, L69 3GE, United Kingdom

Location

University Hospital Aintree

Liverpool, Merseyside, L9 7AL, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

All patients will have a 15 ml blood sample taken for glucose, insulin, lipid profile and liver function tests (LFTs). Insulin sensitivity will be measured by HOMA-IR. Plasma concentrations of FGF-21 will be measured using a commercial ELISA kit (Human FGF-21; Biovendor, Germany). 16 GHD patients, who are eligible for GH replacement therapy as part of their routine clinical care, according to the National Institute for Clinical Excellence (NICE) recommendations, based on the biochemical deficiency and the appropriate AGHDA questionnaire score (AGHDA score\>11) will also be re-tested following 6-months of growth hormone replacement therapy

MeSH Terms

Conditions

Dwarfism, Pituitary

Condition Hierarchy (Ancestors)

Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hypopituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Officials

• Daniel J Cuthbertson, PhD

  University of Liverpool

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2014
• First Posted: September 18, 2014
• Study Start: September 1, 2014
• Primary Completion: August 1, 2015
• Study Completion: June 6, 2017
• Last Updated: December 18, 2024

Record last verified: 2014-09

Locations

GB (2)