Clinical trial NCT01814540: Bovine Milk Oligosaccharide Study
Official title: Pilot Study: Tolerability of Feeding Different Doses of Bovine Milk Oligosaccharides for Modifying Gastrointestinal Function in Healthy Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Dairy Research Institute
First posted: 2013-03-20
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to elucidate tolerability and effectiveness in consumption of the complex indigestible sugars from dairy products called bovine milk oligosaccharides (BMO) to enrich intestinal microflora toward beneficial populations.

Detailed description: This is a single-blind crossover study designed to determine if BMO at two different doses selectively enrich beneficial bacteria in the human gut and will be tolerated in healthy participants compared with a placebo control supplement. Each participant will consume two sachets of supplement for eleven days, separated by a two-week washout before starting the second and third arms. To determine the effect of dose, the placebo-control supplement will be administered in the first arm, followed by the low and high dose. Participants will collect stool and first morning urine and study personnel collected blood from each participant at baseline (day 0) and at the end (Day 11) of each study arm for all three arms.

Eligibility criteria: Inclusion Criteria:

* Healthy men and women aged 18-40 years old
* BMI 18-25
* Born by vaginal birth (not C-section)
* Breastfed for a minimum of 2 months after birth

Exclusion Criteria:

* Individuals who regularly consume high fiber cereals or fiber supplements
* Individuals who frequently consume yogurt (eligible if willing to refrain consumption during the study period)
* Individuals who are lactose intolerant and/or allergic to dairy or wheat
* Individuals who use tobacco products
* Individuals who are pregnant or lactating
* Individuals with a known presence of gastrointestinal/malabsorption disorders or autoimmune disease
* Individuals taking prescription or over-the-counter medications that include pre/probiotics, corticosteroids, anti-obesity agents, laxatives, and lipid- altering medications

Primary outcomes:
measure: Gut microbiota
timeFrame: Change from baseline to day 11
Secondary outcomes:
measure: Urinary Metabolites
timeFrame: Days 0, 4, 11
measure: Plasma Lipid Profile
timeFrame: Day 0 and Day 11
measure: Plasma Glucose
timeFrame: Day 0 and Day 11
measure: Dietary Macronutrient Intake
timeFrame: Day 0
measure: Gut Tolerability
timeFrame: Days Minus 7 and Days 0-10
measure: Stool Consistency
timeFrame: Minus Day 7 and Days 0-10
measure: Fecal BMO
timeFrame: Days 0, 4 and 11
measure: Fecal Metatranscriptome
timeFrame: Days 0 and 11
Other outcomes:
Locations:
city: Davis
country: United States
facility: University of California, Davis
state: California
Study officials:
affiliation: University of California, Davis
name: Daniela Barile, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: Jennifer Smilowitz, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: J. Bruce German, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: Carolyn Slupsky, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: Angela M Zivkovic, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: David A Mills, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pedersen A, Sandstrom B, Van Amelsvoort JM. The effect of ingestion of inulin on blood lipids and gastrointestinal symptoms in healthy females. Br J Nutr. 1997 Aug;78(2):215-22. doi: 10.1079/bjn19970141.
citation: Tao N, DePeters EJ, Freeman S, German JB, Grimm R, Lebrilla CB. Bovine milk glycome. J Dairy Sci. 2008 Oct;91(10):3768-78. doi: 10.3168/jds.2008-1305.
citation: Tao N, DePeters EJ, German JB, Grimm R, Lebrilla CB. Variations in bovine milk oligosaccharides during early and middle lactation stages analyzed by high-performance liquid chromatography-chip/mass spectrometry. J Dairy Sci. 2009 Jul;92(7):2991-3001. doi: 10.3168/jds.2008-1642.
citation: Barile D, Tao N, Lebrilla CB, Coisson JD, Arlorio M, German JB. Permeate from cheese whey ultrafiltration is a source of milk oligosaccharides. Int Dairy J. 2009 Sep 1;19(9):524-530. doi: 10.1016/j.idairyj.2009.03.008.
citation: Barile D, Marotta M, Chu C, Mehra R, Grimm R, Lebrilla CB, German JB. Neutral and acidic oligosaccharides in Holstein-Friesian colostrum during the first 3 days of lactation measured by high performance liquid chromatography on a microfluidic chip and time-of-flight mass spectrometry. J Dairy Sci. 2010 Sep;93(9):3940-9. doi: 10.3168/jds.2010-3156.
citation: Strum JS, Aldredge D, Barile D, Lebrilla CB. Coupling flash liquid chromatography with mass spectrometry for enrichment and isolation of milk oligosaccharides for functional studies. Anal Biochem. 2012 May 15;424(2):87-96. doi: 10.1016/j.ab.2012.02.012. Epub 2012 Feb 25.
citation: Sundekilde UK, Barile D, Meyrand M, Poulsen NA, Larsen LB, Lebrilla CB, German JB, Bertram HC. Natural variability in bovine milk oligosaccharides from Danish Jersey and Holstein-Friesian breeds. J Agric Food Chem. 2012 Jun 20;60(24):6188-96. doi: 10.1021/jf300015j. Epub 2012 Jun 6.
citation: Zivkovic AM, Barile D. Bovine milk as a source of functional oligosaccharides for improving human health. Adv Nutr. 2011 May;2(3):284-9. doi: 10.3945/an.111.000455. Epub 2011 Apr 30.
citation: Garrido D, Barile D, Mills DA. A molecular basis for bifidobacterial enrichment in the infant gastrointestinal tract. Adv Nutr. 2012 May 1;3(3):415S-21S. doi: 10.3945/an.111.001586.
citation: Aldredge DL, Geronimo MR, Hua S, Nwosu CC, Lebrilla CB, Barile D. Annotation and structural elucidation of bovine milk oligosaccharides and determination of novel fucosylated structures. Glycobiology. 2013 Jun;23(6):664-76. doi: 10.1093/glycob/cwt007. Epub 2013 Feb 22.
citation: Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997 Sep;32(9):920-4. doi: 10.3109/00365529709011203.
citation: Smilowitz JT, Lemay DG, Kalanetra KM, Chin EL, Zivkovic AM, Breck MA, German JB, Mills DA, Slupsky C, Barile D. Tolerability and safety of the intake of bovine milk oligosaccharides extracted from cheese whey in healthy human adults. J Nutr Sci. 2017 Feb 20;6:e6. doi: 10.1017/jns.2017.2. eCollection 2017.