Diabetes Mellitus Type INCT02077348
Metabolic Signalling in Muscle- and Adipose-tissue Following Insulin Withdrawal and Growth Hormone Injection.
A study testing Insulin withdrawal and Norditropin in people with Diabetes Mellitus Type I and Ketoacidosis, run by University of Aarhus at 1 site in Denmark.
Trial summary
Diabetes mellitus type I (DM I) is characterized by lack of endogenous insulin and these patients are 100% dependent on insulin substitution to survive. Insulin is a potent anabolic hormone with its primary targets in the liver, the skeletal muscle-tissue and - adipose-tissue. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Diabetes Mellitus Type I, Ketoacidosis
- What is being tested?
- Insulin withdrawal and Norditropin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteDenmark
- Study dates
- May 2014to Sep 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Diabetes Mellitus Type I, C-peptide negative, 19 < BMI < 26, Written consent -
Who cannot join
- Ischemic heart disease, Cardiac arrythmia, Epilepsy, Other medical illness
- -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Metabolic Signalling in Muscle- and Adipose Tissue Following Insulin Withdrawal and Growth Hormone Injection in Type I Diabetes Mellitus, a Clinical Experimental Study.
Diabetes mellitus type I (DM I) is characterized by lack of endogenous insulin and these patients are 100% dependent on insulin substitution to survive.
Insulin is a potent anabolic hormone with its primary targets in the liver, the skeletal muscle-tissue and - adipose-tissue.
Read more
Severe lack of insulin leads to elevated blood glucose levels, dehydration, electrolyte derangement, ketosis and thus eventually ketoacidosis.
Insulin signalling pathways are well-known.
Growth hormone (GH) is also a potent anabolic hormone, responsible for human growth and preservation of protein during fasting. GH (in concert with lack of insulin) induces lipolysis during fasting. It is not known how GH exerts its lipolytic actions.
The aim is to define insulin and growth hormone (GH) signalling pathways in 3 different states in patients with DM I.
And to test whether ATGL-related lipolysis in adipose tissue contributes to the development of ketosis.
- Good glycemic control
- Lack of insulin (ketosis/ketoacidosis)
- Good glycemic control and GH injection
Read the detailed description
Diabetes mellitus type I (DMI ) is characterized by lack of endogenous insulin and these patients are 100% dependent on insulin substitution to survive.
Insulin is a potent anabolic hormone with its primary targets in- the liver, -the skeletal muscle-tissue and - fat-tissue.
In the liver it enhances glycogenesis and inhibits glycogenolysis and gluconeogenesis.
In skeletal muscle-tissue, it enhances glucose transport into the cell, glycogenesis, glycolysis, glucose oxidation and protein synthesis.
In fat-tissue, it inhibits lipolysis and enhances lipogenesis.
This indicates that a fall in serum insulin levels lead to increased blood glucose and increased levels of FFA's (free fatty acids) in the blood - eventually leading to ketone production.
If this condition is not corrected, it will lead to ketoacidosis, which is a potentially life-threatening condition, that is to be corrected under hospital admission with fluid-therapy, electrolyte- and insulin-substitution.
Insulin has been studied thoroughly and signalling pathways are well known.
An interesting pathway is suppression of lipolysis. The most important and rate-limiting lipase in triglyceride hydrolysis is adipose triglyceride lipase (ATGL)(1-5). A connection between ATGL and G0/G1 switch gene (G0S2) has been shown (6,7). During lipolysis ATGL is up-regulated and G0S2 is down-regulated and the promoter region for G0S2 has binding-sites for glucose, insulin dependent transcription factors and peroxisome proliferator-activated receptors y (PPAR-y)(8).
One former study has shown that fasting reduces G0S2 and increases ATGL in humane adipose-tissue(7).
The anti-lipolytic effects of insulin, could be thought, to be mediated through increased transcription of G0S2 which then in turn inhibits ATGL. Conversely, increased lipolysis during lack of insulin.
Growth hormone and growth hormone dependent synthesis og IGF-1 (Insulin-like growth factor - 1) is crucial for human growth before and during adolescence. As an adult GH and IGF-1 are still potent growth factors and also they exert essential regulatory properties on human metabolism(9,10)
GH- signalling pathways go through the GH-receptor, which phosphorylates and thus activates the receptor associated Janus Kinase 2 (JAK2). The signals from this point have been examined in numerous studies.
In rodents, the signal has been shown to run three ways (9,10) Studies on human fibroblast cells have been able to support two of these pathways (MAPK - mitogen-activated protein kinase and STAT - signal transducer and activator of transcription), but not through the insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3-K) pathway.
In human (in vivo) studies, GH stimulation and phosphorylation of STAT5 has been evident, however an association between GH stimulation and activation of MAPK and PI3-K has not been shown (11).
The latter is interesting and remarkable, considering the insulin-agonistic and antagonistic effects of GH.
GH stimulates lipolysis, but exactly how the lipolytic properties of GH are mediated is not fully understood. However, it is shown that GH has an effect on hormone-sensitive lipase (12) (HSL).
Other options could be, as found in rodents, interaction via PI3-K signaling pathway or via G0S2/ATGL interaction, either directly or perhaps mediated through IGF-1.
Humane intracellular signaling-pathways during development of ketosis/ketoacidosis are not well-known. The investigators believe that understanding these pathways and the exact mechanisms behind the development of ketoacidosis, is of great importance.
- Conditions
- Diabetes Mellitus Type I, Ketoacidosis
- Being tested
- Insulin withdrawal, Norditropin
- Keywords
- Diabetes Mellitus type I, Ketoacidosis, Insulin withdrawal, Growth hormone injection, Lipolysis and ATGL
- Medical subject headings
- Diabetes Mellitus, Type 1, Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin withdrawalDrug
Also called Insuman Rapid
Withdrawal of usual (evening) insulin, replaced by Insuman Rapid (10% of the amount of usual evening insulin) as a continuous IV- administration overnight until 8 o'clock on the study day.
NorditropinDrug
Also called Growth Hormone
0,4 mg of GH administered at 7.05 A.M. on the study day.
| Study group | Role | What they receive |
|---|---|---|
| Insulin | No intervention | good glycemic control: 50 % of the subject's basal insulin dosage will be given as a continuous IV administration of insuman rapid overnight (hospitalized and fasting from 10 p.m.) and on the study-day. Basal period from 7.00 am to 12.00pm. The subject will undergo a hyperinsulinemic euglycemic clamp from 12.00 pm to 2.30 pm. Three muscle- and three fat-biopsies will be obtained. A palmitic-acid tracer, a glucose tracer, urea tracer, tyrosine- and phenylalanine- tracers will be given. |
| Insulin withdrawal | Experimental | 10 % of the individual subject's regular insulin dosage will be given as a continuous IV administration of insuman rapid overnight (hospitalized and fasting from 10 p.m.) Basal period from 7.00 am to 12.00 pm (without insulin). The subject will undergo a hyperinsulinemic euglycemic clamp from 12.00 pm to 2.30 pm.
Three muscle- and three fat-biopsies will be obtained. A palmitic-acid tracer, a glucose tracer, urea tracer, tyrosine- and phenylalanine- tracers will be given. Receives: Drug: Insulin withdrawal |
| Norditropin (Growth Hormone) | Experimental | Same amount of insulin administered on the control day (good glycemic control) overnight and on the study day (hospitalized and fasting from 10 p.m.). On the study day, a bolus injection of 0,4 mg of growth hormone (Norditropin) will be administered at 7.05 am. Basal period from 7.00 am to 12.00 pm (good glycemic control).The subject will undergo a hyperinsulinemic euglycemic clamp from 12.00 pm to 2.30 pm.
Three muscle- and three fat-biopsies will be obtained. A palmitic-acid tracer, a glucose tracer, urea tracer, tyrosine- and phenylalanine- tracers will be given. Receives: Drug: Norditropin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin and growth hormone signalling, expressed as CHANGE in phosphorylation of intracellular target proteins and CHANGE in mRNA expression of target genes in muscle- and fat-tissue.
Change in phosphorylation of target proteins and mRNA (messenger RNA) expression of target genes assessed with western blotting technique.
Measured: Muscle and fat biopsies obtained on each study day (arm): t1= 7.00 (0 min) am t2=11.30 (270min) am t3= 13.00 pm (360min)
Secondary outcomes (3)
Change in Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies.
Assessed by Western blotting.
Measured: Muscle and fat biopsies obtained on each study day (arm): t1= 7.00 (0 min) am t2=11.30 (270min) am t3= 13.00 pm (360min)
Metabolism
Change in glucose, fat and protein metabolism assessed by tracer kinetics on every study day (specific times below) and by indirect calorimetry.
[3H 3]Glucose tracer from t=80min - 260min. [9,10-3H]Palmitic acid tracer from t=200min - 260min. [13C] Urea tracer from 20min - 260min.
15N-phenylalanine tracer and 2H4-tyrosine tracer from 80 min - 260 min.
Measured: Change in glucose, fat and protein metabolism between study days.
Ghrelin
Change in circulating plasma acyl- and desacyl ghrelin levels between study days.
Measured: Plasma samples obtained at t=0, t=15, t=30, t=45, t=60, t=75, t=90, t=105, t=120, t=150, t=180, t=210, t=240, t=270, t=300
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2014 (estimated)
- Study startMay 2014
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus Type IStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas Schmidt Voss, University of Aarhus
- Investigators
- Niels Møller, MD, Study chair, Aarhus University / Aarhus University HospitalThomas Voss, MD, Principal investigator, Aarhus University / Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02077348
- Sponsor's protocol ID
- 1-10-72-247-13
- Other IDs
- 1-10-72-247-13
- Status last verified
- Feb 2016
- First submitted
- 20 Feb 2014
- Last updated
- 24 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Bezaire V, Mairal A, Ribet C, Lefort C, Girousse A, Jocken J, Laurencikiene J, Anesia R, Rodriguez AM, Ryden M, Stenson BM, Dani C, Ailhaud G, Arner P, Langin D. Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes. J Biol Chem. 2009 Jul 3;284(27):18282-91. doi: 10.1074/jbc.M109.008631. Epub 2009 May 11.
PubMed 19433586Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J, Heldmaier G, Maier R, Theussl C, Eder S, Kratky D, Wagner EF, Klingenspor M, Hoefler G, Zechner R. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science. 2006 May 5;312(5774):734-7. doi: 10.1126/science.1123965.
PubMed 16675698Langin D, Dicker A, Tavernier G, Hoffstedt J, Mairal A, Ryden M, Arner E, Sicard A, Jenkins CM, Viguerie N, van Harmelen V, Gross RW, Holm C, Arner P. Adipocyte lipases and defect of lipolysis in human obesity. Diabetes. 2005 Nov;54(11):3190-7. doi: 10.2337/diabetes.54.11.3190.
PubMed 16249444Schweiger M, Schreiber R, Haemmerle G, Lass A, Fledelius C, Jacobsen P, Tornqvist H, Zechner R, Zimmermann R. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. J Biol Chem. 2006 Dec 29;281(52):40236-41. doi: 10.1074/jbc.M608048200. Epub 2006 Oct 30.
PubMed 17074755Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M, Lass A, Neuberger G, Eisenhaber F, Hermetter A, Zechner R. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science. 2004 Nov 19;306(5700):1383-6. doi: 10.1126/science.1100747.
PubMed 15550674Yang X, Lu X, Lombes M, Rha GB, Chi YI, Guerin TM, Smart EJ, Liu J. The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab. 2010 Mar 3;11(3):194-205. doi: 10.1016/j.cmet.2010.02.003.
PubMed 20197052Nielsen TS, Vendelbo MH, Jessen N, Pedersen SB, Jorgensen JO, Lund S, Moller N. Fasting, but not exercise, increases adipose triglyceride lipase (ATGL) protein and reduces G(0)/G(1) switch gene 2 (G0S2) protein and mRNA content in human adipose tissue. J Clin Endocrinol Metab. 2011 Aug;96(8):E1293-7. doi: 10.1210/jc.2011-0149. Epub 2011 May 25.
PubMed 21613358Teunissen BE, Smeets PJ, Willemsen PH, De Windt LJ, Van der Vusse GJ, Van Bilsen M. Activation of PPARdelta inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts. Cardiovasc Res. 2007 Aug 1;75(3):519-29. doi: 10.1016/j.cardiores.2007.04.026. Epub 2007 May 3.
PubMed 17543901Birzniece V, Sata A, Ho KK. Growth hormone receptor modulators. Rev Endocr Metab Disord. 2009 Jun;10(2):145-56. doi: 10.1007/s11154-008-9089-x.
PubMed 18622706Moller 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 19240267Silva CM, Kloth MT, Whatmore AJ, Freeth JS, Anderson N, Laughlin KK, Huynh T, Woodall AJ, Clayton PE. GH and epidermal growth factor signaling in normal and Laron syndrome fibroblasts. Endocrinology. 2002 Jul;143(7):2610-7. doi: 10.1210/endo.143.7.8909.
PubMed 12072393Beauville M, Harant I, Crampes F, Riviere D, Tauber MT, Tauber JP, Garrigues M. Effect of long-term rhGH administration in GH-deficient adults on fat cell epinephrine response. Am J Physiol. 1992 Sep;263(3 Pt 1):E467-72. doi: 10.1152/ajpendo.1992.263.3.E467.
PubMed 1415526Fisker FA, Voss TS, Svart MV, Kampmann U, Vendelbo MH, Bengtsen MB, Lauritzen ES, Moller N, Jessen N. Insulin Signaling Is Preserved in Skeletal Muscle During Early Diabetic Ketoacidosis. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e155-e162. doi: 10.1210/clinem/dgad464.
PubMed 37554078Lauritzen ES, Svart MV, Voss T, Moller N, Bjerre M. Impact of Acutely Increased Endogenous- and Exogenous Ketone Bodies on FGF21 Levels in Humans. Endocr Res. 2021 Feb;46(1):20-27. doi: 10.1080/07435800.2020.1831015. Epub 2020 Oct 19.
PubMed 33074729Voss TS, Vendelbo MH, Kampmann U, Pedersen SB, Nielsen TS, Johannsen M, Svart MV, Jessen N, Moller N. Substrate metabolism, hormone and cytokine levels and adipose tissue signalling in individuals with type 1 diabetes after insulin withdrawal and subsequent insulin therapy to model the initiating steps of ketoacidosis. Diabetologia. 2019 Mar;62(3):494-503. doi: 10.1007/s00125-018-4785-x. Epub 2018 Dec 1.
PubMed 30506451
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metabolic Signalling in Muscle- and Adipose Tissue Following Insulin Withdrawal and Growth Hormone Injection in Type I Diabetes Mellitus, a Clinical Experimental Study.
- ClinicalTrials.gov ID
- NCT02077348
- Acronym / sponsor ID
- 1-10-72-247-13
- Conditions
- Diabetes Mellitus Type I, Ketoacidosis
- Keywords
- Diabetes Mellitus type I, Ketoacidosis, Insulin withdrawal, Growth hormone injection, Lipolysis and ATGL
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 4 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diabetes mellitus type I (DM I) is characterized by lack of endogenous insulin and these patients are 100% dependent on insulin substitution to survive.
Insulin is a potent anabolic hormone with its primary targets in the liver, the skeletal muscle-tissue and - adipose-tissue.
Severe lack of insulin leads to elevated blood glucose levels, dehydration, electrolyte derangement, ketosis and thus eventually ketoacidosis.
Insulin signalling pathways are well-known.
Growth hormone (GH) is also a potent anabolic hormone, responsible for human growth and preservation of protein during fasting. GH (in concert with lack of insulin) induces lipolysis during fasting. It is not known how GH exerts its lipolytic actions.
The aim is to define insulin and growth hormone (GH) signalling pathways in 3 different states in patients with DM I.
And to test whether ATGL-related lipolysis in adipose tissue contributes to the development of ketosis.
- Good glycemic control
- Lack of insulin (ketosis/ketoacidosis)
- Good glycemic control and GH injection
Detailed description
Diabetes mellitus type I (DMI ) is characterized by lack of endogenous insulin and these patients are 100% dependent on insulin substitution to survive.
Insulin is a potent anabolic hormone with its primary targets in- the liver, -the skeletal muscle-tissue and - fat-tissue.
In the liver it enhances glycogenesis and inhibits glycogenolysis and gluconeogenesis.
In skeletal muscle-tissue, it enhances glucose transport into the cell, glycogenesis, glycolysis, glucose oxidation and protein synthesis.
In fat-tissue, it inhibits lipolysis and enhances lipogenesis.
This indicates that a fall in serum insulin levels lead to increased blood glucose and increased levels of FFA's (free fatty acids) in the blood - eventually leading to ketone production.
If this condition is not corrected, it will lead to ketoacidosis, which is a potentially life-threatening condition, that is to be corrected under hospital admission with fluid-therapy, electrolyte- and insulin-substitution.
Insulin has been studied thoroughly and signalling pathways are well known.
An interesting pathway is suppression of lipolysis. The most important and rate-limiting lipase in triglyceride hydrolysis is adipose triglyceride lipase (ATGL)(1-5). A connection between ATGL and G0/G1 switch gene (G0S2) has been shown (6,7). During lipolysis ATGL is up-regulated and G0S2 is down-regulated and the promoter region for G0S2 has binding-sites for glucose, insulin dependent transcription factors and peroxisome proliferator-activated receptors y (PPAR-y)(8).
One former study has shown that fasting reduces G0S2 and increases ATGL in humane adipose-tissue(7).
The anti-lipolytic effects of insulin, could be thought, to be mediated through increased transcription of G0S2 which then in turn inhibits ATGL. Conversely, increased lipolysis during lack of insulin.
Growth hormone and growth hormone dependent synthesis og IGF-1 (Insulin-like growth factor - 1) is crucial for human growth before and during adolescence. As an adult GH and IGF-1 are still potent growth factors and also they exert essential regulatory properties on human metabolism(9,10)
GH- signalling pathways go through the GH-receptor, which phosphorylates and thus activates the receptor associated Janus Kinase 2 (JAK2). The signals from this point have been examined in numerous studies.
In rodents, the signal has been shown to run three ways (9,10) Studies on human fibroblast cells have been able to support two of these pathways (MAPK - mitogen-activated protein kinase and STAT - signal transducer and activator of transcription), but not through the insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3-K) pathway.
In human (in vivo) studies, GH stimulation and phosphorylation of STAT5 has been evident, however an association between GH stimulation and activation of MAPK and PI3-K has not been shown (11).
The latter is interesting and remarkable, considering the insulin-agonistic and antagonistic effects of GH.
GH stimulates lipolysis, but exactly how the lipolytic properties of GH are mediated is not fully understood. However, it is shown that GH has an effect on hormone-sensitive lipase (12) (HSL).
Other options could be, as found in rodents, interaction via PI3-K signaling pathway or via G0S2/ATGL interaction, either directly or perhaps mediated through IGF-1.
Humane intracellular signaling-pathways during development of ketosis/ketoacidosis are not well-known. The investigators believe that understanding these pathways and the exact mechanisms behind the development of ketoacidosis, is of great importance.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Insulin | No intervention | –good glycemic control: 50 % of the subject's basal insulin dosage will be given as a continuous IV administration of insuman rapid overnight (hospitalized and fasting from 10 p.m.) and on the study-day. Basal period from 7.00 am to 12.00pm. The subject will undergo a hyperinsulinemic euglycemic clamp from 12.00 pm to 2.30 pm. Three muscle- and three fat-biopsies will be obtained. A palmitic-acid tracer, a glucose tracer, urea tracer, tyrosine- and phenylalanine- tracers will be given. |
| Insulin withdrawal | Experimental | Drug: Insulin withdrawal10 % of the individual subject's regular insulin dosage will be given as a continuous IV administration of insuman rapid overnight (hospitalized and fasting from 10 p.m.) Basal period from 7.00 am to 12.00 pm (without insulin). The subject will undergo a hyperinsulinemic euglycemic clamp from 12.00 pm to 2.30 pm. Three muscle- and three fat-biopsies will be obtained. A palmitic-acid tracer, a glucose tracer, urea tracer, tyrosine- and phenylalanine- tracers will be given. |
| Norditropin (Growth Hormone) | Experimental | Drug: NorditropinSame amount of insulin administered on the control day (good glycemic control) overnight and on the study day (hospitalized and fasting from 10 p.m.). On the study day, a bolus injection of 0,4 mg of growth hormone (Norditropin) will be administered at 7.05 am. Basal period from 7.00 am to 12.00 pm (good glycemic control).The subject will undergo a hyperinsulinemic euglycemic clamp from 12.00 pm to 2.30 pm. Three muscle- and three fat-biopsies will be obtained. A palmitic-acid tracer, a glucose tracer, urea tracer, tyrosine- and phenylalanine- tracers will be given. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Diagnosis of Diabetes Mellitus Type I, C-peptide negative, 19 < BMI < 26, Written consent -
Key exclusion criteria (2 listed)
- Ischemic heart disease, Cardiac arrythmia, Epilepsy, Other medical illness
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insulin withdrawalAlso: Insuman RapidWithdrawal of usual (evening) insulin, replaced by Insuman Rapid (10% of the amount of usual evening insulin) as a continuous IV- administration overnight until 8 o'clock on the study day. | Drug | Insulin withdrawal |
| NorditropinAlso: Growth Hormone0,4 mg of GH administered at 7.05 A.M. on the study day. | Drug | Norditropin (Growth Hormone) |
Primary outcome
Insulin and growth hormone signalling, expressed as CHANGE in phosphorylation of intracellular target proteins and CHANGE in mRNA expression of target genes in muscle- and fat-tissue.
Time frame: Muscle and fat biopsies obtained on each study day (arm): t1= 7.00 (0 min) am t2=11.30 (270min) am t3= 13.00 pm (360min)
Change in phosphorylation of target proteins and mRNA (messenger RNA) expression of target genes assessed with western blotting technique.
3 secondary outcomes
Change in Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies.
Time frame: Muscle and fat biopsies obtained on each study day (arm): t1= 7.00 (0 min) am t2=11.30 (270min) am t3= 13.00 pm (360min)
Metabolism
Time frame: Change in glucose, fat and protein metabolism between study days.
Ghrelin
Time frame: Plasma samples obtained at t=0, t=15, t=30, t=45, t=60, t=75, t=90, t=105, t=120, t=150, t=180, t=210, t=240, t=270, t=300
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2016.
- Background: PubMed 19433586Bezaire V, Mairal A, Ribet C, Lefort C, Girousse A, Jocken J, Laurencikiene J, Anesia R, Rodriguez AM, Ryden M, Stenson BM, Dani C, Ailhaud G, Arner P, Langin D. Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes. J Biol Chem. 2009 Jul 3;284(27):18282-91. doi: 10.1074/jbc.M109.008631. Epub 2009 May 11.
- Background: PubMed 16675698Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J, Heldmaier G, Maier R, Theussl C, Eder S, Kratky D, Wagner EF, Klingenspor M, Hoefler G, Zechner R. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science. 2006 May 5;312(5774):734-7. doi: 10.1126/science.1123965.
- Background: PubMed 16249444Langin D, Dicker A, Tavernier G, Hoffstedt J, Mairal A, Ryden M, Arner E, Sicard A, Jenkins CM, Viguerie N, van Harmelen V, Gross RW, Holm C, Arner P. Adipocyte lipases and defect of lipolysis in human obesity. Diabetes. 2005 Nov;54(11):3190-7. doi: 10.2337/diabetes.54.11.3190.
- Background: PubMed 17074755Schweiger M, Schreiber R, Haemmerle G, Lass A, Fledelius C, Jacobsen P, Tornqvist H, Zechner R, Zimmermann R. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. J Biol Chem. 2006 Dec 29;281(52):40236-41. doi: 10.1074/jbc.M608048200. Epub 2006 Oct 30.
- Background: PubMed 15550674Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M, Lass A, Neuberger G, Eisenhaber F, Hermetter A, Zechner R. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science. 2004 Nov 19;306(5700):1383-6. doi: 10.1126/science.1100747.
- Background: PubMed 20197052Yang X, Lu X, Lombes M, Rha GB, Chi YI, Guerin TM, Smart EJ, Liu J. The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab. 2010 Mar 3;11(3):194-205. doi: 10.1016/j.cmet.2010.02.003.
- Background: PubMed 21613358Nielsen TS, Vendelbo MH, Jessen N, Pedersen SB, Jorgensen JO, Lund S, Moller N. Fasting, but not exercise, increases adipose triglyceride lipase (ATGL) protein and reduces G(0)/G(1) switch gene 2 (G0S2) protein and mRNA content in human adipose tissue. J Clin Endocrinol Metab. 2011 Aug;96(8):E1293-7. doi: 10.1210/jc.2011-0149. Epub 2011 May 25.
- Background: PubMed 17543901Teunissen BE, Smeets PJ, Willemsen PH, De Windt LJ, Van der Vusse GJ, Van Bilsen M. Activation of PPARdelta inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts. Cardiovasc Res. 2007 Aug 1;75(3):519-29. doi: 10.1016/j.cardiores.2007.04.026. Epub 2007 May 3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niels Møller, MD study chair
Aarhus University / Aarhus University Hospital
Thomas Voss, MD principal investigator
Aarhus University / Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Insulin withdrawal and Norditropin in people with Diabetes Mellitus Type I and Ketoacidosis, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin and growth hormone signalling, expressed as CHANGE in phosphorylation of intracellular target proteins and CHANGE in mRNA expression of target genes in muscle- and fat-tissue. (time frame: Muscle and fat biopsies obtained on each study day (arm): t1= 7.00 (0 min) am t2=11.30 (270min) am t3= 13.00 pm (360min)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02077348, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2016.