Clinical trial NCT05660278: Comparing the Inflammation, Maldigestion and Symptoms Due to Commercial Milk and A2 Milk
Official title: Comparing the Acute Effects of A1 Containing Commercial Milk and A2 Milk on Inflammation, Lactose Intolerance and Lactose Maldigestion in Lactose Maldigesters
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lactose Intolerance
Lead sponsor: Purdue University
Sponsor class: OTHER
First posted: 2022-12-21
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: Cow's milk contains two types of β-casein: A1 and A2. It is evident from human clinical trials that milk with A1 protein produces more hydrogen and symptoms of lactose intolerance. A pro-inflammatory μ-opioid peptide BCM-7 is released from A1 but not from A2. Milk containing A1 β-casein produced more inflammatory markers than A2 β-casein. This is a double-blinded, randomized, controlled trial conducted to determine if A1 beta-casein containing milk causes acute effects on inflammatory markers following a single milk feeding, as compared to milk containing only A2 beta-casein.

Detailed description: Recruitment:

Flyers, emails, and advertisements in local and university newspapers will be used for recruitment of study participants.

Phone screening:

Interested individuals will be contacted via phone by study staff to assess eligibility by asking questions listed in the inclusion and exclusion criteria.

Informed consent:

If the individual is eligible through phone screening, the study staff will read and explain the informed consent to the individual. Informed consent will contain all the information regarding study procedure, compensation, risks and benefits. If Informed Consent is granted, the participant will be contacted through their preferred method of contact (email or phone) to schedule a hydrogen breath test (HBT).

Screening lactose maldigesters via HBT:

Maldigestion will be classified by a rise of breath hydrogen concentration of greater than 20ppm after a challenge dose of 2% commercial milk containing 0.5g lactose per kg body weight. Participants will consume a low-fiber meal and then fast 12 hours prior to HBT. A breath sample will be obtained from participants just before drinking the milk dose. Participants will then consume milk containing 0.5 grams lactose per kilogram body weight. Breath samples will be obtained according to the following schedule: 0 hour (pre dose), 30 minutes, 1 hour, 90 minutes, 2 hours, 3 hours, 4 hours, 5 hours and 6 hours. Participants who exhibit a rise of breath hydrogen concentration of greater than 20ppm between any two timepoints of the 6-hour test will be classified as lactose maldigesters, and will be qualified to enter the intervention portion of the study.

Intervention:

There will be two in-person visits in intervention. The visits will be at least 6 days apart.

Visit 1:

Participants will consume a low-fiber dinner and fast for 12 hours prior to the visit. Participants will provide their first breath sample before consumption of milk. Participants will then consume a challenge dose of first randomized milk containing 0.5g lactose per kg body weight. Breath samples will be collected at 0 hour (pre dose), 30 minutes, 1 hour, 90 minutes, 2 hours, 3 hours, 4 hours, 5 hours and 6 hours. Participants will be asked to report and rate any symptoms including abdominal pain, bloating, flatulence, fecal urgency, and diarrhea they might experience during the 6 hour test.Blood will be drawn from participants at 0 hour (pre-dose), 1 hour , 2 hours and 3 hours time-point via catheter and serum will be isolated from whole blood for analyses of markers including hs-CRP, IgG, IgG1, Il-4, GSH and BCM-7.

Visit 2:

There will be at least a 6-day interval between Visit 1 and Visit 2. The same procedure from visit 1 will be followed in visit 2. Participants will consume the second randomized milk containing 0.5 grams lactose per kilogram body weight during this visit.

Eligibility criteria: Inclusion Criteria:

* • Ability/desire to provide informed consent

  * Aged 18 to 65 years of age inclusive at screening
  * Current or recent history of intolerance to or avoidance of dairy of at least one month duration (by self-report and self-reported symptoms).
  * Agrees to refrain from all other treatments and products used for dairy intolerance (e.g., Lactaid® Dietary Supplements) during study involvement
  * Willing to return for all study visits and complete all study related procedures
  * Able to understand and provide written informed consent in English

Exclusion Criteria:

* • Allergic to milk

  * Currently pregnant
  * Currently lactating
  * Cigarette smoking or other use of tobacco or nicotine containing products within 3 months of screening
  * 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
  * 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 \[Note: history of uncomplicated abdominal surgeries such as removal of an appendix more than 12 months prior to screening will not be excluded\]
  * 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.
  * Active ulcers, or history of severe ulcers
  * Diabetes mellitus (type 1 and type 2)
  * Congestive Heart Failure (CHF)
  * Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C
  * Height: ___ Weight: ___ BMI: ___

    o Weighing \<16.5 kg and BMI \> 35 kg/m2
  * Recent bowel preparation for endoscopic or radiologic investigation within four weeks of screening (e.g., colonoscopy prep)
  * Use of concurrent therapy(ies) or other products (e.g., laxatives, stool softeners, Pepto Bismol®, Lactaid® Dietary Supplements) used for symptoms of dairy intolerance within 7 days of screening
  * Chronic antacid and/or PPI use
  * Recent use of systemic antibiotics defined as use within 30 days prior to screening
  * Recent high colonic enema, defined as use within 30 days prior to screening
  * Any concurrent disease or symptoms which may interfere with the assessment of the cardinal
  * symptoms of dairy intolerance (i.e., gas, diarrhea, bloating, cramps, stomach pain)
  * History of ethanol (alcohol) and/or drug abuse in the past 12 months
  * Currently undergoing chemotherapy
  * Use of any investigational drug or participation in any investigational study within 30 days prior to screening
  * Prior enrollment in this study
  * Any other conditions/issues noted by the study staff and/or Principal Investigator that would impact participation and/or protocol compliance

Primary outcomes:
measure: Difference in inflammation between commercial and A2 milk
timeFrame: Within the 3 hours following milk dose
measure: Difference in hydrogen between commercial and A2 milk
timeFrame: Within the 6 hours following milk dose
measure: Difference in symptoms between commercial and A2 milk
timeFrame: Within the 6 hours following milk dose
Secondary outcomes:
Other outcomes:
Locations:
city: West Lafayette
country: United States
facility: Purdue University
state: Indiana
Study officials:
affiliation: Purdue University
name: Dennis Savaiano, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jianqin S, Leiming X, Lu X, Yelland GW, Ni J, Clarke AJ. Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk. Nutr J. 2016 Apr 2;15:35. doi: 10.1186/s12937-016-0147-z.
citation: Ramakrishnan M, Eaton TK, Sermet OM, Savaiano DA. Milk Containing A2 beta-Casein ONLY, as a Single Meal, Causes Fewer Symptoms of Lactose Intolerance than Milk Containing A1 and A2 beta-Caseins in Subjects with Lactose Maldigestion and Intolerance: A Randomized, Double-Blind, Crossover Trial. Nutrients. 2020 Dec 17;12(12):3855. doi: 10.3390/nu12123855.
citation: Cieslinska A, Kostyra E, Kostyra H, Olenski K, Fiedorowicz E, Kaminski S. Milk from cows of different beta-casein genotypes as a source of beta-casomorphin-7. Int J Food Sci Nutr. 2012 Jun;63(4):426-30. doi: 10.3109/09637486.2011.634785. Epub 2011 Nov 14.