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

NCT05660278 | Unknown DMC

• 1 other identifier: IRB-2022-845
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Lactose Intolerance

Outcome Measures

Primary Outcomes (3)

• 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.

  Within the 3 hours following milk dose

• Difference in hydrogen between commercial and A2 milk

  Hydrogen concentration (ppm) will be measured in breath sample using a hydrogen breath analyzer.

  Within the 6 hours following milk dose

• 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).

  Within the 6 hours following milk dose

Interventions

Milk containing A1 and A2 beta-casein OTHER

Single dose of milk

Also known as: Commercial milk

Milk containing only A2 beta-casein OTHER

Single dose of milk

Also known as: A2 milk

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Purdue University: lead

Study Sites (1)

Purdue University

West Lafayette, Indiana, 47906, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 27039383 BACKGROUND

• 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.

  PMID: 33348621 BACKGROUND

• 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.

  PMID: 22080615 BACKGROUND

MeSH Terms

Conditions

Lactose Intolerance

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Dennis Savaiano, PhD

  Purdue University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dennis Savaiano, PhD

CONTACT

494-8228; savaiano@purdue.edu

Tracy Eaton, MSW

CONTACT

tkeaton@purdue.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 7, 2022
• First Posted: December 21, 2022
• Study Start: January 18, 2022
• Primary Completion: December 1, 2024
• Study Completion: August 1, 2025
• Last Updated: December 21, 2022

Record last verified: 2022-12

Locations

US (1)