Clinical trial NCT03713346: Comparing the Digestion of Milk With Different Beta-casein Protein Content by Dairy Intolerant Persons
Official title: Comparing the Digestion of Milk With Different Beta-casein Protein Content by Dairy Intolerant Persons
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dairy Intolerance
Keywords: lactose
dairy
intolerance
Lead sponsor: Purdue University
Sponsor class: OTHER
First posted: 2018-10-19
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: Persons with dairy intolerance may experience cramps/abdominal pain, bloating, flatulence, acute diarrhea, or fecal urgency when they ingest excessive amounts of lactose. The intensity of these conditions can be mild or severe and likely depends on numerous variables including dose, transit time, intestinal residual lactase activity and microbiome potential to ferment lactose. Jersey cattle produce milk containing high levels of the A2 β-casein protein . There are claims that high A2 β-casein milk is more easily digested by people who are lactose maldigesters . We propose to conduct a double-blinded, randomized, controlled trial to determine if high A2 β-casein milk from Jersey cattle is actually better digested and tolerated by lactose maldigesters.

Detailed description: Persons with dairy intolerance may experience cramps/abdominal pain, bloating, flatulence, acute diarrhea, or fecal urgency when they ingest excessive amounts of lactose. The intensity of these conditions can be mild or severe and likely depends on numerous variables including dose, transit time, intestinal residual lactase activity and microbiome potential to ferment lactose. Jersey cattle produce milk containing high levels of the A2 β-casein protein . There are claims that high A2 β-casein milk is more easily digested by people who are lactose maldigesters . We propose to conduct a double-blinded, randomized, controlled trial to determine if high A2 β-casein milk from Jersey cattle is actually better digested and tolerated by lactose maldigesters.

This proposed protocol comparing the dairy intolerance symptoms from milks containing predominantly the A1 variant versus A2 variant will establish if high A2 milk is better digested and/or tolerated than high A1 milk.

Participants will be asked to consume four different commercially available milks in random order. The samples will be fed for breakfast separated by at least 10 days, after overnight fasts. The commercial milk treatments will include; high A1 β-casein milk (commercial milk), high A2 β-casein milk, Jersey cattle milk (which contains a mixture of A1 and A2 β-casein), and a lactose free milk control. Milk will be 2% fat content to control for transit. Each subject will be fed milk containing 0.5g lactose per kg body weight. There will be two arms in this study: dairy intolerant who are lactose maldigesters, and dairy intolerant who are lactose digesters.

Eligibility criteria: Inclusion Criteria:

1. Ability/desire to provide informed consent
2. Aged 18 to 65 years of age inclusive at screening
3. Current or recent history of intolerance to and avoidance of milk of at least one month duration (by self-report and self-reported symptoms).
4. Agrees to refrain from all other treatments and products used for lactose intolerance (e.g., Lactaid® Dietary Supplements) during study involvement
5. Willing to return for all study visits and complete all study related procedures, including fasting before and during the hydrogen breath tests
6. Qualifying Lactose Challenge Symptom Score:

(4 symptom categories with severity measured on from 0 to 5) as defined by one of the following:

1. At least one score of "moderately severe" or "severe" on a single symptom during the 6 hour HBT test;
2. A score of "moderate" or greater for a single symptom on at least two (2) time points during the 6 hour HBT test;
3. At least one "moderate" score or greater on each of two symptoms during the 6 hour HBT test 7. Hydrogen concentration of at least 20 parts per million greater than baseline at least 2 time points during the screening hydrogren breath test 8. Able to understand and provide written informed consent in English

Exclusion Criteria:

1. Allergic to milk
2. Currently pregnant
3. Currently lactating
4. Cigarette smoking or other use of tobacco or nicotine containing products within 3 months of screening
5. Diagnosed with any of the following disorders known to be associated with abnormal gastrointestinal motility such as; Gastroparesis, amyloidosis, neuromuscular diseases (including Parkinson's disease), collagen vascular diseases, alcoholism, uremia, malnutrition, or untreated hypothyroidism
6. History of surgery that alters the normal function of the gastrointestinal tract including, but not limited to: gastrointestinal bypass surgery, bariatric surgery, gastric banding, vagotomy, fundoplication, pyloroplasty \[Note: history of uncomplicated abdominal surgeries such as removal of an appendix more than 12 months prior to screening will not be excluded\]
7. Past or present : Organ transplant, chronic pancreatitis, pancreatic insufficiency, symptomatic biliary disease, Celiac disease, chronic constipation, diverticulosis, inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), small intestine bacterial overgrowth syndrome (SIBO), gastroparesis, gastro-esophageal reflux disease (GERD), Irritable Bowel Syndrome (IBS) or any other medical condition with symptoms that could confound collection of adverse events.
8. Active ulcers, or history of severe ulcers
9. Diabetes mellitus (type 1 and type 2)
10. Congestive Heart Failure (CHF)
11. Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C
12. BMI \> 35 kg/m2
13. Recent bowel preparation for endoscopic or radiologic investigation within four weeks of screening (e.g., colonoscopy prep)
14. Use of concurrent therapy(ies) or other products (e.g., laxatives, stool softeners, Pepto Bismol®, Lactaid® Dietary Supplements) used for symptoms of lactose intolerance within 7 days of screening
15. Chronic antacid and/or PPI use
16. Recent use of systemic antibiotics defined as use within 30 days prior to screening
17. Recent high colonic enema, defined as use within 30 days prior to screening
18. Any concurrent disease or symptoms which may interfere with the assessment of the cardinal symptoms of lactose intolerance (i.e., gas, diarrhea, bloating, cramps, stomach pain)
19. History of ethanol (alcohol) and/or drug abuse in the past 12 months
20. Currently undergoing chemotherapy
21. Use of any investigational drug or participation in any investigational study within 30 days prior to screening
22. Prior enrollment in this study
23. Any other conditions/issues noted by the study staff and/or Principal Investigator that would impact participation and/or protocol compliance

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Primary outcomes:
measure: Differences in AUC ΔH2 concentrations
timeFrame: Within the 6 hours following the milk challenge
Secondary outcomes:
measure: Differences within each of the symptom categories
timeFrame: Within the 6 hours following the milk challenge
Other outcomes:
Locations:
city: West Lafayette
country: United States
facility: Purdue University
state: Indiana
Study officials:
affiliation: Purdue University
name: Dennis A Savaiano, PhD
role: PRINCIPAL_INVESTIGATOR
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