Impact of A2 Milk Versus Conventional Milk on Intestinal Health: a Proof-of-concept Study in IBS-patients

• ClinicalTrials.gov Identifier: NCT04598529
• Recruitment Status: Not yet recruiting
• First Posted: October 22, 2020
• Last Update Posted: September 8, 2021
• Sponsor: Maastricht University Medical Center
• Information provided by (Responsible Party): Maastricht University Medical Center

Study Description

Brief Summary:

This aim of this study is to evaluate the acute and mid-term effects of A2 milk versus conventional milk on gastrointestinal symptoms in patients with constipation-predominant IBS and in patients with diarrhea-predominant IBS. Moreover, the effect of immune and defense markers will be studied.

Condition or disease	Intervention/treatment	Phase
Irritable Bowel Syndrome	Other: A2 milk; Other: Conventional milk	Not Applicable

Detailed Description:

Irritable bowel syndrome (IBS) is a prevalent functional bowel disorder in which recurrent abdominal pain is associated with defecation and altered bowel habits. Although the pathophysiology is incompletely understood, it is generally regarded as a multifactorial disorder involving host factors such as low-grade immune activation, altered intestinal barrier function and defense. Environmental factors, including diet, are also suggested to play a role. Dairy products such as cow's milk are widely produced and an important component of the human diet. Cow's milk is composed of various macronutrients, micronutrients and water. Beta-casein is a major protein component of cow's milk; most cows produce a mixture of A1 and A2 beta-casein (conventional milk), whereas some cows produce only A2 beta-casein (A2 milk). It has been suggested that specific components in cow's milk, such as A1 beta-casein, may trigger gastrointestinal symptoms after intake.

The purpose of this randomized, double-blind, cross-over study performed in Maastricht University Medical Center (MUMC+) is to explore the acute and mid-terms effects of A2 milk versus conventional milk on gastrointestinal symptoms and immune and defense markers in separate groups of patient with constipation-predominant IBS and in patients with diarrhea-predominant IBS.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Impact of A2 Milk Versus Conventional Milk on Intestinal Health: a Proof-of-concept Study in Irritable Bowel Syndrome Patients
• Estimated Study Start Date: October 2021
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: A2 milk; A2 milk, organic, 200ml, twice daily	Other: A2 milk; a variety of cow's milk that contains only A2 beta-casein (and therefore lacks of A1 beta-casein).
Placebo Comparator: Conventional milk; Pasteurized semi-skimmed milk, organic, 200ml, twice daily	Other: Conventional milk; cow's milk with a mixture of A1 and A2 beta-casein.

Outcome Measures

Primary Outcome Measures :

1. The acute effects of A2 milk versus conventional milk on overall gastrointestinal discomfort in separate groups of individuals with IBS-C and IBS-D. [ Time Frame: day 1 of each intervention period ]
   Assessed by a single item using a visual analogue scale (VAS), anchored at the low end (score of 0) with the absence of overall symptoms and at the other end (score of 100) with severe symptoms, the worst it has ever been.

Secondary Outcome Measures :

1. The mid-term effects of A2 milk versus conventional milk on overall gastrointestinal discomfort in separate groups of individuals with IBS-C and IBS-D. [ Time Frame: up to 14 days (once daily) of each intervention period ]
   Assessed by a single item using a visual analogue scale (VAS), anchored at the low end (score of 0) with the absence of overall symptoms and at the other end (score of 100) with severe symptoms, the worst it has ever been.
2. The acute and mid-term effects of A2 milk versus conventional milk on single gastrointestinal symptoms and stool characteristics in separate groups of individuals with IBS-C and IBS-D. [ Time Frame: multiple times at day 1 and once daily at day 2-14 of each intervention period ]
   Assessed by a visual analogue scale (VAS) for different gastrointestinal symptoms, anchored at the low end (score of 0) with the absence of overall symptoms and at the other end (score of 100) with severe symptoms, the worst it has ever been.
3. The mid-term effects of A2 milk versus conventional milk on single gastrointestinal symptoms and stool characteristics in separate groups of individuals with IBS-C and IBS-D. [ Time Frame: day 1 and 14 of each intervention period ]
   Assessed by the IBS-SSS questionnaire (a 0-100 scale, with the total IBS-SSS score ranging between 0 and 500, with higher scores indicating more severe symptoms).
4. The mid-term effects of A2 milk versus conventional milk on gastrointestinal immune and defense markers in separate groups of individuals with IBS-C and IBS-D. [ Time Frame: day 1 and 14 of each intervention period ]
   Assessed by several parameters of GI immune and defense in feces.
5. The mid-term effects of A2 milk versus conventional milk on gastrointestinal immune and defense markers in separate groups of individuals with IBS-C and IBS-D. [ Time Frame: day 1 and 14 of each intervention period ]
   Assessed by several parameters of GI immune and defense in blood.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• IBS with constipation (IBS-C) or IBS with diarrhea (IBS-D), based on the Rome IV criteria
• Self-reported indication that dietary components (e.g. milk) trigger GI symptoms
• Body Mass Index (BMI) < 30 kg/m2
• Weight-stable for at least 90 days prior to participation (no change in bodyweight, i.e. < 3kg).
• Willing to be informed in case of unexpected findings.

Exclusion Criteria:

• History of any disease or surgery interfering with the study aims, limiting participating or completing the study protocol
• Self-admitted human immunodeficiency virus-positive state.
• Disease with a life expectancy shorter than 5 years.
• Abdominal surgery interfering with gastrointestinal function (to be decided by a medical doctor)
• Based on anamnesis, patients with lactose intolerance will be excluded. If not tested before, a lactose breath test can be performed to check for lactose intolerance.
• Self reported cow's milk allergy
• Use of antibiotics within 30 days prior to the study
• Use of other medication interfering with study outcomes, as will be reviewed by a medical doctor, who will decide on in- or exclusion based on the drug(s) used
• Administration of probiotic or prebiotic supplements, investigational drugs or participation in any scientific intervention study, which may interfere with this study (to be decided by the principle investigator), in the 14 days prior to the study
• Known pregnancy or lactation
• Plan to loose weight or follow a specific diet within the study period
• Alcohol intake: female >7 units/week for females, male >14 units/week
• Blood donation within 1 month prior to the study
• Insufficient fluency of the Dutch language

Contacts and Locations

Contacts

Contact: Michelle Bosman, MD; +31(0)433884291; m.bosman@maastrichtuniversity.nl

Contact: D.M.A.E. Jonkers, Prof. Dr.; d.jonkers@maastrichtuniversity.nl

Sponsors and Collaborators

Maastricht University Medical Center

Investigators

• Principal Investigator: A.M.M. Masclee, Prof. Dr.; Maastricht University Medical Center

More Information

• Responsible Party: Maastricht University Medical Center
• ClinicalTrials.gov Identifier: NCT04598529
• Other Study ID Numbers: NL73898.068.20; METC 20-032 ( Other Identifier: Medical Ethical Committee )
• First Posted: October 22, 2020
• Last Update Posted: September 8, 2021
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Currently, we do not anticipate on sharing data outside MUMC+. If this changes in the future, we will submit an amendment.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Maastricht University Medical Center:

Irritable Bowel Syndrome; IBS-C; IBS-D; Conventional milk; A2 milk; Gastrointestinal symptoms

Additional relevant MeSH terms:

Irritable Bowel Syndrome; Syndrome; Disease; Pathologic Processes; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases