HypopituitarismNCT02782208
Lipolytic Effects of GH in Hypopituitary Patients in Vivo
A study testing Acipimox, GH substitution and GH pause in people with Hypopituitarism and Insulin Resistance, run by University of Aarhus at 1 site in Denmark.
Trial summary
Growth hormone (GH) is essential for longitudinal bone growth and somatic development. These protein anabolic effects require sufficient nutritional supply. During fasting and caloric restriction GH predominantly promotes fat metabolism. Read more about this study
- Who is it for?
- Ages 18 to 70 years, men only
- Conditions the study is for
- Hypopituitarism, Insulin Resistance, Endocrine System Diseases
- What is being tested?
- Acipimox, GH substitution and GH pause
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteDenmark
- Study dates
- 10 Feb 2016to 22 Dec 2016
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- hypopituitary patients with documented GH-deficiency
Who cannot join
- other significant disease
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Lipolytic Effects of GH in Hypopituitary Patients in Vivo: Molecular Mechanisms and Temporal Patterns.
Growth hormone (GH) is essential for longitudinal bone growth and somatic development. These protein anabolic effects require sufficient nutritional supply. During fasting and caloric restriction GH predominantly promotes fat metabolism.
GH counteracts the effect of insulin in many tissues, of which insulin-stimulated glucose uptake in skeletal muscle has been most extensively studied. Substrate competition between elevated free fatty acids and glucose is suggested as a mechanism, and this hypothesis can be tested mechanistically by means of acipimox, which is a nicotinic acid that suppresses the fat metabolizing effects of GH.
Read more
The hypothesis is, that the suppressive effect of GH on insulin-stimulated glucose uptake in skeletal muscle is obviated by acipimox-induced inhibition of fat metabolism.
In order to investigate this, eight adult hypopituitary patients with documented GH-deficiency will be studied in the presence and absence of GH and acipimox, respectively, and biopsies from skeletal muscle and subcutaneous adipose tissue will be analyzed.
Knowledge of the effects of growth hormone and fat metabolism can in shot-sight as well as in long-sight have great importance for the understanding of growth disorders from overweight and type 2 diabetes to malnutrition and eating disorders.
- Conditions
- Hypopituitarism, Insulin Resistance, Endocrine System Diseases, Glucose Metabolism Disorders, Metabolic Diseases, Pituitary Diseases
- Being tested
- Acipimox, Placebo, GH substitution, GH pause
- Medical subject headings
- Hypopituitarism, Insulin Resistance, Endocrine System Diseases, Glucose Metabolism Disorders, Metabolic Diseases, Pituitary Diseases, Brain Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcipimoxDrug
Also called Olbetam
Acipimox is administered 4 times previous to and during the investigation day. Acipimox is used to suppress the lipolytic effect of GH.
PlaceboDrug
Placebo is administered 4 times previous to and during the investigation day.
GH substitutionDrug
GH substitution as usually
GH pauseOther
GH substitution pause two days prior to the experimental day
| Study group | Role | What they receive |
|---|---|---|
| Acipimox/GH substitution | Active comparator | Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Continue GH substitution as usually. Receives: Drug: Acipimox; Drug: GH substitution |
| Acipimox/GH pause | Active comparator | Drug: Acipimox Tablet Acipimox 250 mg administered 4 times previous to and during the investigation day Other Name: Tablet Olbetam 250 mg Pause GH substitution to days prior to the study day. Receives: Drug: Acipimox; Other: GH pause |
| Placebo/GH substitution | Placebo comparator | Drug: Placebo tablets Continue GH substitution as usually. Receives: Drug: Placebo; Drug: GH substitution |
| Placebo/GH pause | Placebo comparator | Drug: Placebo tablets Pause GH substitution to days prior to the study day. Receives: Drug: Placebo; Other: GH pause |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lipolytic activity measured as area under the curve (AUC) for FFA (free fatty acid) before and during clamp-conditions.
Measured: 1 year
Secondary outcomes (4)
GH signaling proteins and gene targets in adipose and skeletal muscle tissues measured by western blotting and qPCR
Measured: 1,5 years
Insulin sensitivity as measured by M value and GIR (glucose infusion rate)
Measured: 6 months
Substrate metabolism as measured by indirect calorimetry, tritiated glucose and circulating hormones and metabolites
Measured: 1 year
PDH (pyruvate dehydrogenase) activity in skeletal muscle measured by an PDH activity assay
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2016 (estimated)
- Study start10 Feb 2016
- Primary completion22 Dec 2016
- Study completion22 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for HypopituitarismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jens Otto L Jørgensen, Professor, Principal investigator, University Hospital of Aarhus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02782208
- Sponsor's protocol ID
- GHD01
- Status last verified
- Oct 2017
- First submitted
- 18 May 2016
- Last updated
- 26 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Tunaru S, Kero J, Schaub A, Wufka C, Blaukat A, Pfeffer K, Offermanns S. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med. 2003 Mar;9(3):352-5. doi: 10.1038/nm824. Epub 2003 Feb 3.
PubMed 12563315Nellemann 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.
PubMed 24148194Clasen BF, Poulsen MM, Escande C, Pedersen SB, Moller N, Chini EN, Jessen N, Jorgensen JO. Growth hormone signaling in muscle and adipose tissue of obese human subjects: associations with measures of body composition and interaction with resveratrol treatment. J Clin Endocrinol Metab. 2014 Dec;99(12):E2565-73. doi: 10.1210/jc.2014-2215.
PubMed 25050904Krusenstjerna-Hafstrom T, Clasen BF, Moller N, Jessen N, Pedersen SB, Christiansen JS, Jorgensen JO. Growth hormone (GH)-induced insulin resistance is rapidly reversible: an experimental study in GH-deficient adults. J Clin Endocrinol Metab. 2011 Aug;96(8):2548-57. doi: 10.1210/jc.2011-0273. Epub 2011 May 25.
PubMed 21613350Nielsen TS, Jessen N, Jorgensen JO, Moller N, Lund S. Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease. J Mol Endocrinol. 2014 Jun;52(3):R199-222. doi: 10.1530/JME-13-0277. Epub 2014 Feb 27.
PubMed 24577718Moller N, Jorgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev. 2009 Apr;30(2):152-77. doi: 10.1210/er.2008-0027. Epub 2009 Feb 24.
PubMed 19240267Nielsen S, Moller N, Christiansen JS, Jorgensen JO. Pharmacological antilipolysis restores insulin sensitivity during growth hormone exposure. Diabetes. 2001 Oct;50(10):2301-8. doi: 10.2337/diabetes.50.10.2301.
PubMed 11574412Hjelholt AJ, Charidemou E, Griffin JL, Pedersen SB, Gudiksen A, Pilegaard H, Jessen N, Moller N, Jorgensen JOL. Insulin resistance induced by growth hormone is linked to lipolysis and associated with suppressed pyruvate dehydrogenase activity in skeletal muscle: a 2 x 2 factorial, randomised, crossover study in human individuals. Diabetologia. 2020 Dec;63(12):2641-2653. doi: 10.1007/s00125-020-05262-w. Epub 2020 Sep 18.
PubMed 32945898