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Non-alcoholic Fatty Liver DiseaseNCT02337660

Involvement of Steatosis-induced Glucagon Resistance in Hyperglucagonaemia

A study testing Liver biopsy and Pancreatic clamp in people with Non-alcoholic Fatty Liver Disease, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to examine whether non-alcoholic fatty liver disease (NAFLD) is associated with hepatic glucagon resistance and hyperglucagonemia. Read more about this study

Who is it for?
Ages 25 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Non-alcoholic Fatty Liver Disease
What is being tested?
Liver biopsy and Pancreatic clamp
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteDenmark
Study dates
Jan 2015to Jan 2016
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 25 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Normal fasting plasma glucose and HbA1c < 6.0%
  • Between 18.5 and 25 kg/m2 or between 30 and 40 kg/m2
  • Normal haemoglobin
  • Normal coagulation factor II, VII and X, INR and thrombocytes
  • Age above 25 years
  • Informed consent

Who cannot join

  • Diabetes
  • Prediabetes (impaired glucose tolerance and/or impaired fasting plasma glucose)
  • First-degree relatives with diabetes
  • Nephropathy (eGFR < 60ml/min and/or albuminuria)
  • Liver disease (ALAT and/or serum ASAT >2x normal values)
  • Use of anticoagulative medicine like Clopidogrel og Warfarin
Show all 9Show fewer
  • Pregnancy and/or breastfeeding
  • Age above 80 years
  • Any condition that the investigator feels would interfere with trial participation

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Center for Diabetes Research

    Gentofte Municipality, 2900

Other trials in Denmark

About this study

The purpose of this study is to examine whether non-alcoholic fatty liver disease (NAFLD) is associated with hepatic glucagon resistance and hyperglucagonemia.

Read the detailed description

Hyperglucagonemia is a common condition in obesity, prediabetes and type 2 diabetes. It increases the hepatic glucose production, thus contributing to type 2-diabetic hyperglycemia. In the current study we wish to examine whether non-alcoholic fatty disease (NAFLD) results in hepatic glucagon resistance. This could result in hyperglucagonemia through a feedback mechanism acting on the level of pancreatic alpha cells. Cirrhosis and type 1 diabetes, respectively, has previously been shown to be associated with hepatic glucagon resistance but it has not been examined in relation to NAFLD in humans so far.

Being tested
Liver biopsy, Pancreatic clamp
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Liver biopsyProcedure or surgery

    One ultrasound guided liver biopsy

  • Pancreatic clampOther

    I.v. infusions of somatostatin and insulin (basal rate) for will be adminstered for 3 hours. Glucagon will administered for 3 hours in total with infusion rates at a basal and a high physiological rate for 1.5 hours each.

Study groups in NCT02337660
Study groupRoleWhat they receive
Healthy, leanExperimental15 healthy, lean subjects. Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
Receives: Procedure: Liver biopsy; Other: Pancreatic clamp
Obese, otherwise healthyExperimental15 obese, otherwise healthy subjects Will have a liver biopsy, and on the experimental day a pancreatic clamp will be performed.
Receives: Procedure: Liver biopsy; Other: Pancreatic clamp

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Endogenous glucose production

    Measured: 0-180 min

  2. Amino acid metabolism

    Measured: 0-180 min

Secondary outcomes (2)

  1. Degree of steatosis

    Measured: baseline

  2. Total RNA sequencing of liver biopsies

    Measured: baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2015 (estimated)
  2. Study startJan 2015
  3. Primary completionJan 2016
  4. Study completionJan 2016

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02337660
Sponsor's protocol ID
SIRG-1
Status last verified
Nov 2018
First submitted
8 Jan 2015
Last updated
16 Nov 2018
Results posted
No
Data monitoring committee
No

Publications

  • Mitrakou A, Kelley D, Veneman T, Jenssen T, Pangburn T, Reilly J, Gerich J. Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM. Diabetes. 1990 Nov;39(11):1381-90. doi: 10.2337/diab.39.11.1381.

    PubMed 2121568

  • Gromada J, Franklin I, Wollheim CB. Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev. 2007 Feb;28(1):84-116. doi: 10.1210/er.2006-0007. Epub 2007 Jan 16.

    PubMed 17261637

  • Knop FK, Aaboe K, Vilsboll T, Volund A, Holst JJ, Krarup T, Madsbad S. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes Obes Metab. 2012 Jun;14(6):500-10. doi: 10.1111/j.1463-1326.2011.01549.x. Epub 2012 Jan 17.

    PubMed 22171657

  • Faerch K, Pilgaard K, Knop FK, Hansen T, Pedersen O, Jorgensen T, Holst JJ. Incretin and pancreatic hormone secretion in Caucasian non-diabetic carriers of the TCF7L2 rs7903146 risk T allele. Diabetes Obes Metab. 2013 Jan;15(1):91-5. doi: 10.1111/j.1463-1326.2012.01675.x. Epub 2012 Sep 9.

    PubMed 22862926

  • Mitrakou A, Kelley D, Mokan M, Veneman T, Pangburn T, Reilly J, Gerich J. Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. N Engl J Med. 1992 Jan 2;326(1):22-9. doi: 10.1056/NEJM199201023260104.

    PubMed 1727062

  • Unger RH, Orci L. The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet. 1975 Jan 4;1(7897):14-6. doi: 10.1016/s0140-6736(75)92375-2.

    PubMed 46337

  • Liljenquist JE, Mueller GL, Cherrington AD, Keller U, Chiasson J-L, Perry JM, Lacy WW, Rabinowitz D. Evidence for an important role of glucagon in the regulation of hepatic glucose production in normal man. J Clin Invest. 1977 Feb;59(2):369-74. doi: 10.1172/JCI108649.

    PubMed 833282

  • Ferrannini E, Muscelli E, Natali A, Gabriel R, Mitrakou A, Flyvbjerg A, Golay A, Hojlund K; Relationship between Insulin Sensitivity and Cardiovascular Disease Risk (RISC) Project Investigators. Association of fasting glucagon and proinsulin concentrations with insulin resistance. Diabetologia. 2007 Nov;50(11):2342-7. doi: 10.1007/s00125-007-0806-x. Epub 2007 Sep 11.

    PubMed 17846745

  • Charbonneau A, Couturier K, Gauthier MS, Lavoie JM. Evidence of hepatic glucagon resistance associated with hepatic steatosis: reversal effect of training. Int J Sports Med. 2005 Jul-Aug;26(6):432-41. doi: 10.1055/s-2004-821225.

    PubMed 16037884

  • Longuet C, Robledo AM, Dean ED, Dai C, Ali S, McGuinness I, de Chavez V, Vuguin PM, Charron MJ, Powers AC, Drucker DJ. Liver-specific disruption of the murine glucagon receptor produces alpha-cell hyperplasia: evidence for a circulating alpha-cell growth factor. Diabetes. 2013 Apr;62(4):1196-205. doi: 10.2337/db11-1605. Epub 2012 Nov 16.

    PubMed 23160527

  • Bhathena SJ, Voyles NR, Smith S, Recant L. Decreased glucagon receptors in diabetic rat hepatocytes. Evidence for regulation of glucagon receptors by hyperglucagonemia. J Clin Invest. 1978 Jun;61(6):1488-97. doi: 10.1172/JCI109069.

    PubMed 207737

  • Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993 Nov;42(11):1663-72. doi: 10.2337/diab.42.11.1663.

    PubMed 8405710

  • Jimba S, Nakagami T, Takahashi M, Wakamatsu T, Hirota Y, Iwamoto Y, Wasada T. Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Diabet Med. 2005 Sep;22(9):1141-5. doi: 10.1111/j.1464-5491.2005.01582.x.

    PubMed 16108839

  • Gupte P, Amarapurkar D, Agal S, Baijal R, Kulshrestha P, Pramanik S, Patel N, Madan A, Amarapurkar A, Hafeezunnisa. Non-alcoholic steatohepatitis in type 2 diabetes mellitus. J Gastroenterol Hepatol. 2004 Aug;19(8):854-8. doi: 10.1111/j.1440-1746.2004.03312.x.

    PubMed 15242486

  • Akbar DH, Kawther AH. Nonalcoholic fatty liver disease in Saudi type 2 diabetic subjects attending a medical outpatient clinic: prevalence and general characteristics. Diabetes Care. 2003 Dec;26(12):3351-2. doi: 10.2337/diacare.26.12.3351-a. No abstract available.

    PubMed 14633828

Questions about this trial

What is this clinical trial studying?

A study testing Liver biopsy and Pancreatic clamp in people with Non-alcoholic Fatty Liver Disease, run by University Hospital, Gentofte, Copenhagen 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 6 inclusion and 9 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 16 Nov 2018. 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?

Endogenous glucose production (time frame: 0-180 min). The study lists 2 primary outcomes in all. 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 NCT02337660, which also lists 20 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 16 Nov 2018.

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