Effects of Growth Hormone and IGF-1 on Anabolic Signals and Stem Cell Recruitment in Human Skeletal Muscle

NCT03878992 | Unknown DMC

• 1 other identifier: GHDSCs
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

Growth Hormone Deficiency; Growth Hormone Treatment

Keywords

Growth hormone; Satellite cells; Metabolism; insulin-like effects

Outcome Measures

Primary Outcomes (1)

• Phosphorylation of Akt in muscle biopsies

  Muscle biopsies will be analysed for phosphorylation of Akt

  Analyses will be performed through study completion, an expected average of 1.5 years

Secondary Outcomes (7)

• Satellite cell count

  Analyses will be performed through study completion, an expected average of 1.5 year

• Satellite cell proliferation and differentiation in cell culture

  Analyses will be performed through study completion, an expected average of 1.5 year

• Strength of muscle

  Analyses will be performed through study completion, an expected average of 1.5 year

• Muscle mass

  Analyses will be performed through study completion, an expected average of 1.5 year

• Glucose turnover rate

  Analyses will be performed through study completion, an expected average of 1.5 year

Study Arms (1)

GHD

OTHER

GHD patients will be studied two times - one time before initiation of GH replacement therapy and one time following three months of GH replacement therapy. The two trial days are identical

Drug: Genotropin miniquick 0.5 mg, injection

Interventions

Genotropin miniquick 0.5 mg, injection DRUG

GH will be given as an injection. Muscle biopsy will be obtained from m. vests laterals of the dominant leg. Fat biopsies will be obtained from subcutaneous abdominal fat. Tracers will be given as a bolus followed by continuous infusion for 6 hours. For palmitate tracer the infusion will be for only 1,5 hours followed by a one hour break and then another 1 hour infusion. Blood tests will be drawn from a venous catheter placed on the dorsal side of the hand.

Also known as: Muscle biopsy, fat biopsy, blood tests, pletysmography, Tracers of metabolism, infusion

GHD

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed adult onset growth hormone deficiency

You may not qualify if:

• Documentation of Growth hormone deficiency for less than three months
• Pregnancy

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator

Study Sites (1)

Department of Endcrinology

Aarhus N, 8200, Denmark

RECRUITING

Related Publications (12)

• Zurlo F, Larson K, Bogardus C, Ravussin E. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest. 1990 Nov;86(5):1423-7. doi: 10.1172/JCI114857.

  PMID: 2243122 BACKGROUND

• DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes. 1981 Dec;30(12):1000-7. doi: 10.2337/diab.30.12.1000. No abstract available.

  PMID: 7030826 BACKGROUND

• Nellemann B, Vendelbo MH, Nielsen TS, Bak AM, Hogild M, Pedersen SB, Bienso RS, Pilegaard H, Moller N, Jessen N, Jorgensen JO. Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity. Acta Physiol (Oxf). 2014 Feb;210(2):392-402. doi: 10.1111/apha.12183. Epub 2013 Nov 22.

  PMID: 24148194 BACKGROUND

• Salomon F, Cuneo RC, Hesp R, Sonksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med. 1989 Dec 28;321(26):1797-803. doi: 10.1056/NEJM198912283212605.

  PMID: 2687691 BACKGROUND

• Rosenbaum M, Gertner JM, Leibel RL. Effects of systemic growth hormone (GH) administration on regional adipose tissue distribution and metabolism in GH-deficient children. J Clin Endocrinol Metab. 1989 Dec;69(6):1274-81. doi: 10.1210/jcem-69-6-1274.

  PMID: 2685009 BACKGROUND

• Pochini L, Oppedisano F, Indiveri C. Reconstitution into liposomes and functional characterization of the carnitine transporter from renal cell plasma membrane. Biochim Biophys Acta. 2004 Feb 10;1661(1):78-86. doi: 10.1016/j.bbamem.2003.12.001.

  PMID: 14967477 BACKGROUND

• Ridderstrale M. Signaling mechanism for the insulin-like effects of growth hormone--another example of a classical hormonal negative feedback loop. Curr Drug Targets Immune Endocr Metabol Disord. 2005 Mar;5(1):79-92. doi: 10.2174/1568008053174787.

  PMID: 15777207 BACKGROUND

• Vahl N, Jorgensen JO, Jurik AG, Christiansen JS. Abdominal adiposity and physical fitness are major determinants of the age associated decline in stimulated GH secretion in healthy adults. J Clin Endocrinol Metab. 1996 Jun;81(6):2209-15. doi: 10.1210/jcem.81.6.8964853.

  PMID: 8964853 BACKGROUND

• Vahl N, Jorgensen JO, Skjaerbaek C, Veldhuis JD, Orskov H, Christiansen JS. Abdominal adiposity rather than age and sex predicts mass and regularity of GH secretion in healthy adults. Am J Physiol. 1997 Jun;272(6 Pt 1):E1108-16. doi: 10.1152/ajpendo.1997.272.6.E1108.

  PMID: 9227458 BACKGROUND

• Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebaek NE, Hilsted J, Skakkebae NE. Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J Clin Endocrinol Metab. 1995 Apr;80(4):1407-15. doi: 10.1210/jcem.80.4.7536210.

  PMID: 7536210 BACKGROUND

• Meinhardt UJ, Ho KK. Modulation of growth hormone action by sex steroids. Clin Endocrinol (Oxf). 2006 Oct;65(4):413-22. doi: 10.1111/j.1365-2265.2006.02676.x.

  PMID: 16984231 BACKGROUND

• Ullman M, Oldfors A. Effects of growth hormone on skeletal muscle. I. Studies on normal adult rats. Acta Physiol Scand. 1989 Apr;135(4):531-6. doi: 10.1111/j.1748-1716.1989.tb08612.x.

  PMID: 2735197 BACKGROUND

MeSH Terms

Conditions

Dwarfism, Pituitary

Interventions

Growth Hormone; Injections; Hematologic Tests

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

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Jens Otto Jørgensen, Professor

  Aarhus University Hospital

  STUDY CHAIR

Central Study Contacts

Tine B Billeskov, PhD student

CONTACT

+4560169141; tine@clin.au.dk

Jens Otto Jørgensen, Professor

CONTACT

+4578462025; joj@clin.au.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will be studies two times - one time before initiation of GH replacement therapy and one time following three months of GH replacement therapy. The two times are identical. The trial day includes infusion of tracers (glucose, tyrosine, phenylalanine, urea, palmitate), muscle biopsies, subcutaneous fat biopsies, an intravenous bolus of 0.5 mg GH, indirect calorimetry, plethysmography, blood samples, strength test, DXA scan and spectroscopy of liver and muscle.

Study Record Dates

• First Submitted: March 7, 2019
• First Posted: March 18, 2019
• Study Start: April 30, 2019
• Primary Completion: March 1, 2021
• Study Completion: December 31, 2021
• Last Updated: September 26, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)