Ignite Creation Date:
2025-12-24 @ 3:51 PM
Ignite Modification Date:
2026-02-04 @ 11:59 AM
Study NCT ID:
NCT03878992
Status:
UNKNOWN
Last Update Posted:
2019-09-26
First Post:
2019-03-07
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effects of Growth Hormone and IGF-1 on Anabolic Signals and Stem Cell Recruitment in Human Skeletal Muscle
Sponsor:
University of Aarhus
Organization:
Study Overview
Official Title:
Effects of Growth Hormone and IGF-1 on Anabolic Signals and Stem Cell Recruitment in Human Skeletal Muscle
Status:
UNKNOWN
Status Verified Date:
2019-02
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
12 adult hypopituitary patients with newly diagnosed Growth hormone (GH)-deficiency will be studied two times. The first examinations will be performed shortly after time of diagnose before initiation of exogenous GH treatment, where each subject will receive a single intravenous bolus of 0.5 mg GH. The examination day will be repeated after prolonged GH replacement therapy (\>3 month after treatment initiation).
Detailed Description:
The overarching aim of this project is to investigate the mechanisms underlying loss of muscle mass in adults (sarcopenia) and the therapeutic potential of growth hormone (GH). The underlying hypothesis is that absence of GH and subsequent reduced insulin-like growth factor I (IGF-I) will impair normal proliferation of skeletal muscle stem cells and this is associated with metabolic dysfunction.
GH is an important regulator of substrate metabolism and muscle mass. GH treatment reduces overall fat mass (FM) through lipolytic actions in adipose tissues and decreased adipose tissue triacylglycerol (TAG) synthesis. In skeletal muscle, exogenous GH administration production shifts substrate metabolism from glucose to lipid oxidation. In addition, GH mediates protein anabolic actions by production of IGF-I during sufficient nutrient supply and maintained insulin secretion. Circulating IGF-I is primarily produced in the liver, but animal studies suggest that locally produced autocrine and paracrine IGF-I is sufficient to maintain normal growth.
GH deficiency (GHD) is a rare disorder characterized by the inadequate secretion of GH from the anterior pituitary gland and requires treatment with exogenous GH administration. Cell culture studies demonstrates that GH elicits insulin-like effects in cells deprived of GH. GH exerts its biological effects through binding to site 1 and 2 on the extracellular domain of a preformed GHR dimer. GHR activation initiates auto-phosphorylation of the receptor-associated Janus Kinase 2 (JAK2), which subsequently induces GHR cross-phosphorylation. The insulin-like effects are mediated by tyrosine phosphorylation of downstream targets including insulin receptor substrate-1 (IRS-1) and IRS-2. During physiological conditions, this signaling pathway is inhibited by the actions of a class of proteins known as suppressors of cytokine signaling (SOCSs).
GHD in adults can be acquired as a result of trauma, infection, radiation therapy, or tumor growth within the brain. It is characterized by a number of variable symptoms including reduced energy levels, altered body composition and reduced muscle strength. Satellite cells (SCs), the skeletal muscle stem cells, are essential for muscle regeneration in genetic or autoimmune muscle diseases as well as after ischemic, chemical or mechanical trauma to the myofibers. Furthermore, SCs are the primary source to supply new myonuclei to growing myofibers during non-traumatic mechanical overload. In rats, GH-administration increases number of SCs in cross-sections of muscle fibres22, and fibre type composition in skeletal muscle is altered in animals with GHD. Together these findings indicate an importance of GH and IGF-I stimulation for muscle regeneration.
GH is an important regulator of substrate metabolism and muscle mass. GH treatment reduces overall fat mass (FM) through lipolytic actions in adipose tissues and decreased adipose tissue triacylglycerol (TAG) synthesis. In skeletal muscle, exogenous GH administration production shifts substrate metabolism from glucose to lipid oxidation. In addition, GH mediates protein anabolic actions by production of IGF-I during sufficient nutrient supply and maintained insulin secretion. Circulating IGF-I is primarily produced in the liver, but animal studies suggest that locally produced autocrine and paracrine IGF-I is sufficient to maintain normal growth.
GH deficiency (GHD) is a rare disorder characterized by the inadequate secretion of GH from the anterior pituitary gland and requires treatment with exogenous GH administration. Cell culture studies demonstrates that GH elicits insulin-like effects in cells deprived of GH. GH exerts its biological effects through binding to site 1 and 2 on the extracellular domain of a preformed GHR dimer. GHR activation initiates auto-phosphorylation of the receptor-associated Janus Kinase 2 (JAK2), which subsequently induces GHR cross-phosphorylation. The insulin-like effects are mediated by tyrosine phosphorylation of downstream targets including insulin receptor substrate-1 (IRS-1) and IRS-2. During physiological conditions, this signaling pathway is inhibited by the actions of a class of proteins known as suppressors of cytokine signaling (SOCSs).
GHD in adults can be acquired as a result of trauma, infection, radiation therapy, or tumor growth within the brain. It is characterized by a number of variable symptoms including reduced energy levels, altered body composition and reduced muscle strength. Satellite cells (SCs), the skeletal muscle stem cells, are essential for muscle regeneration in genetic or autoimmune muscle diseases as well as after ischemic, chemical or mechanical trauma to the myofibers. Furthermore, SCs are the primary source to supply new myonuclei to growing myofibers during non-traumatic mechanical overload. In rats, GH-administration increases number of SCs in cross-sections of muscle fibres22, and fibre type composition in skeletal muscle is altered in animals with GHD. Together these findings indicate an importance of GH and IGF-I stimulation for muscle regeneration.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: