Clinical trial NCT02796950: The Effect of Acipimox on GLP (Glucagon-like Peptide)-1 Secretion
Official title: The Effect of Acipimox on GLP-1 Secretion in Healthy Subjects: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus Type 2
Keywords: Acipimox
GLP-1
Insulin secretion
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2016-06-13
Enrollment: 8
Sex: MALE
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Glucagon like peptide 1 is produced in enteroendocrine L cells in the small intestine stimulated by peroral food intake. GLP-1 induces insulin secretion, and analogues are used in the treatment of DM2 (type 2 diabetes mellitus). Recently it was found, that levels of GLP-1 are increased in response to acipimox. The hypothesis is that G protein coupled receptors on enteroendocrine L cells bind acipimox and thereby induce GLP-1 secretion.

In a controlled, open, randomized experiment, eight healthy, overweight men will be studied on an intervention day, where they receive acipimox, and on a control day. The study day includes an OGTT (oral glucose tolerance test), blood samples before and after the OGTT and a biopsy from adipose tissue.


Eligibility criteria: Inclusion Criteria:

* Adult men
* Healthy
* BMI 25-35

Exclusion Criteria:

* Known DM2
* Receiving hypolipidemic drugs

Primary outcomes:
measure: Levels of GLP-1 in plasma
timeFrame: 9 months
Secondary outcomes:
measure: Lipolytic activity in adipose tissue by measuring FFA (free fatty acid) levels
timeFrame: 9 months
measure: Insulin sensitivity by measuring blood glucose after an OGTT
timeFrame: 5 months
Other outcomes:
measure: Insulin secretion by measuring levels of insulin and c-peptid
timeFrame: 9 months
measure: Secretion of the hormones ghrelin, leptin and GIP (gastric inhibitory polypeptide) by measuring hormone levels in plasma
timeFrame: 9 months
Locations:
city: Aarhus
country: Denmark
facility: University Hospital of Aarhus
Study officials:
affiliation: University of Aarhus
name: Jens Otto L Jørgensen, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pais R, Gribble FM, Reimann F. Stimulation of incretin secreting cells. Ther Adv Endocrinol Metab. 2016 Feb;7(1):24-42. doi: 10.1177/2042018815618177.
citation: Iepsen EW, Torekov SS, Holst JJ. Liraglutide for Type 2 diabetes and obesity: a 2015 update. Expert Rev Cardiovasc Ther. 2015;13(7):753-67. doi: 10.1586/14779072.2015.1054810.
citation: 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.
citation: Newman JC, Verdin E. Ketone bodies as signaling metabolites. Trends Endocrinol Metab. 2014 Jan;25(1):42-52. doi: 10.1016/j.tem.2013.09.002. Epub 2013 Oct 18.
citation: Fulcher GR, Walker M, Catalano C, Farrer M, Alberti KG. Acute metabolic and hormonal responses to the inhibition of lipolysis in non-obese patients with non-insulin-dependent (type 2) diabetes mellitus: effects of acipimox. Clin Sci (Lond). 1992 May;82(5):565-71. doi: 10.1042/cs0820565.