Lipolytic Effects of GH in Hypopituitary Patients in Vivo

NCT ID: NCT02782208

Last Updated: 2020-03-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-10

Study Completion Date

2016-12-22

Brief Summary

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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.

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.

Detailed Description

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Conditions

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Hypopituitarism Insulin Resistance Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Pituitary Diseases Brain Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Acipimox/GH substitution

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.

Group Type ACTIVE_COMPARATOR

Acipimox

Intervention Type DRUG

Acipimox is administered 4 times previous to and during the investigation day. Acipimox is used to suppress the lipolytic effect of GH.

GH substitution

Intervention Type DRUG

GH substitution as usually

Acipimox/GH pause

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.

Group Type ACTIVE_COMPARATOR

Acipimox

Intervention Type DRUG

Acipimox is administered 4 times previous to and during the investigation day. Acipimox is used to suppress the lipolytic effect of GH.

GH pause

Intervention Type OTHER

GH substitution pause two days prior to the experimental day

Placebo/GH substitution

Drug: Placebo tablets Continue GH substitution as usually.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo is administered 4 times previous to and during the investigation day.

GH substitution

Intervention Type DRUG

GH substitution as usually

Placebo/GH pause

Drug: Placebo tablets Pause GH substitution to days prior to the study day.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo is administered 4 times previous to and during the investigation day.

GH pause

Intervention Type OTHER

GH substitution pause two days prior to the experimental day

Interventions

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Acipimox

Acipimox is administered 4 times previous to and during the investigation day. Acipimox is used to suppress the lipolytic effect of GH.

Intervention Type DRUG

Placebo

Placebo is administered 4 times previous to and during the investigation day.

Intervention Type DRUG

GH substitution

GH substitution as usually

Intervention Type DRUG

GH pause

GH substitution pause two days prior to the experimental day

Intervention Type OTHER

Other Intervention Names

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Olbetam

Eligibility Criteria

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Inclusion Criteria

* hypopituitary patients with documented GH-deficiency

Exclusion Criteria

* other significant disease
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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University of Aarhus

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jens Otto L Jørgensen, Professor

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Aarhus

Locations

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University Hospital of Aarhus

Aarhus, , Denmark

Site Status

Countries

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Denmark

References

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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.

Reference Type BACKGROUND
PMID: 12563315 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24148194 (View on PubMed)

Clasen 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.

Reference Type BACKGROUND
PMID: 25050904 (View on PubMed)

Krusenstjerna-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.

Reference Type BACKGROUND
PMID: 21613350 (View on PubMed)

Nielsen 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.

Reference Type BACKGROUND
PMID: 24577718 (View on PubMed)

Moller 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.

Reference Type BACKGROUND
PMID: 19240267 (View on PubMed)

Nielsen 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.

Reference Type BACKGROUND
PMID: 11574412 (View on PubMed)

Hjelholt 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.

Reference Type DERIVED
PMID: 32945898 (View on PubMed)

Other Identifiers

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GHD01

Identifier Type: -

Identifier Source: org_study_id

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