Clinical trial NCT01055340: A Study That Will Evaluate Ketogenesis and Glucose-Dependent Insulin Secretion Methodologies in Healthy Male Subjects (MK-0000-159)(COMPLETED)
Official title: A Randomized Clinical Trial to Study Ketogenesis and Glucose-Dependent Insulin Secretion Methodologies in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Obesity
Keywords: Ketogenesis
Glucose-Dependent Insulin Secretion
Graded Glucose Infusion
Oxyntomodulin
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-01-25
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will test the hypotheses that a single dose of oxyntomodulin (OXM) will be neutral or better than placebo in lowering ambient glucose levels during a graded glucose infusion (GGI) and that a single dose of OXM will lead to a statistically significant increase in the sum of the plasma βOHB + AcAc levels compared to placebo.


Eligibility criteria: Inclusion Criteria:

* Subject is judged to be in good health based on medical history, physical examination, and laboratory safety tests
* Subject has a Body Mass Index of ≥27 kg/m\^2 and ≤35 kg/m\^2 and weighs ≥70 kg at the prestudy (screening) visit
* Subject has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months
* Subject is willing to avoid strenuous physical activity (weight lifting, running, bicycling, etc.) for the duration of the study

Exclusion Criteria:

* Subject is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit
* Subject has a history of stroke, chronic seizures, or major neurological disorder
* Subject has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
* Subject has irritable bowel disease, or recurrent occurrences of nausea, vomiting, diarrhea, or abdominal pain
* Subject has a history of hypertension requiring treatment
* Subject has a history of cancer
* Subject has history of diabetes, or family history of diabetes mellitus
* Subject has a history of hypersensitivity to OXM or hemaccel

Primary outcomes:
measure: Ambient plasma glucose concentration during the GGI
timeFrame: Last 160 minutes of OXM/placebo infusion
measure: plasma βOHB + AcAc concentrations
timeFrame: First 300 minutes of OXM/placebo infusion
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Shankar SS, Shankar RR, Mixson LA, Miller DL, Pramanik B, O'Dowd AK, Williams DM, Frederick CB, Beals CR, Stoch SA, Steinberg HO, Kelley DE. Native Oxyntomodulin Has Significant Glucoregulatory Effects Independent of Weight Loss in Obese Humans With and Without Type 2 Diabetes. Diabetes. 2018 Jun;67(6):1105-1112. doi: 10.2337/db17-1331. Epub 2018 Mar 15.
citation: Shankar SS, Shankar RR, Mixson LA, Miller DL, Chung C, Cilissen C, Beals CR, Stoch SA, Steinberg HO, Kelley DE. Linearity of beta-cell response across the metabolic spectrum and to pharmacology: insights from a graded glucose infusion-based investigation series. Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E865-73. doi: 10.1152/ajpendo.00527.2015. Epub 2016 Apr 12.