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Comparing the Inflammation, Maldigestion and Symptoms Due to Commercial Milk and A2 Milk

Primary Purpose

Lactose Intolerance

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Milk containing A1 and A2 beta-casein
Milk containing only A2 beta-casein
Sponsored by
Purdue University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional other trial for Lactose Intolerance

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Purdue UniversityRecruiting

Outcomes

Primary Outcome Measures

Difference in inflammation between commercial and A2 milk
The concentration of inflammatory markers hs-CRP, IL-4, IgG, IgG1, BCM-7, GSH in serum will be measured using ELISA kits, Cobas 400 plus analyzer and a Cobas e411 analyzer in nanometers.
Difference in hydrogen between commercial and A2 milk
Hydrogen concentration (ppm) will be measured in breath sample using a hydrogen breath analyzer.
Difference in symptoms between commercial and A2 milk
Participants will record and rate abdominal pain, bloating, flatulence, diarrhea and fecal urgency using a 6-point Likert Scale during the 6-hour test. The scale ranges from a score of 0 to 5 (0 = none, 1 =slight, 2 = mild, 3 = moderate, 4 = moderately severe, 5 = severe).

Secondary Outcome Measures

Full Information

First Posted
December 7, 2022
Last Updated
December 20, 2022
Sponsor
Purdue University
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1. Study Identification

Unique Protocol Identification Number
NCT05660278
Brief Title
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 18, 2022 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Purdue University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lactose Intolerance

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Other
Intervention Name(s)
Milk containing A1 and A2 beta-casein
Other Intervention Name(s)
Commercial milk
Intervention Description
Single dose of milk
Intervention Type
Other
Intervention Name(s)
Milk containing only A2 beta-casein
Other Intervention Name(s)
A2 milk
Intervention Description
Single dose of milk
Primary Outcome Measure Information:
Title
Difference in inflammation between commercial and A2 milk
Description
The concentration of inflammatory markers hs-CRP, IL-4, IgG, IgG1, BCM-7, GSH in serum will be measured using ELISA kits, Cobas 400 plus analyzer and a Cobas e411 analyzer in nanometers.
Time Frame
Within the 3 hours following milk dose
Title
Difference in hydrogen between commercial and A2 milk
Description
Hydrogen concentration (ppm) will be measured in breath sample using a hydrogen breath analyzer.
Time Frame
Within the 6 hours following milk dose
Title
Difference in symptoms between commercial and A2 milk
Description
Participants will record and rate abdominal pain, bloating, flatulence, diarrhea and fecal urgency using a 6-point Likert Scale during the 6-hour test. The scale ranges from a score of 0 to 5 (0 = none, 1 =slight, 2 = mild, 3 = moderate, 4 = moderately severe, 5 = severe).
Time Frame
Within the 6 hours following milk dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dennis Savaiano, PhD
Phone
494-8228
Ext
765
Email
savaiano@purdue.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Tracy Eaton, MSW
Email
tkeaton@purdue.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dennis Savaiano, PhD
Organizational Affiliation
Purdue University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Purdue University
City
West Lafayette
State/Province
Indiana
ZIP/Postal Code
47906
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dennis Savaiano, PhD
Phone
765-427-7826
Ext
+1
Email
savaiano@purdue.edu
First Name & Middle Initial & Last Name & Degree
Tracy Eaton, MSW
Phone
7654946083
Ext
+1
Email
tkeaton@purdue.edu

12. IPD Sharing Statement

Citations:
PubMed Identifier
27039383
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. Erratum In: Nutr J. 2016;15(1):45.
Results Reference
background
PubMed Identifier
33348621
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.
Results Reference
background
PubMed Identifier
22080615
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.
Results Reference
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Learn more about this trial

Comparing the Inflammation, Maldigestion and Symptoms Due to Commercial Milk and A2 Milk

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