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Comparing the Gastric Transit of Commercial Milk and A2 Milk

Primary Purpose

Lactose Intolerance, Adult Type

Status
Active
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, Adult Type

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 Milk intolerant and identified as a lactose maldigester while participating in the Milk Protein Study (applicable only for subjects from the previous milk protein study and not applicable for new subjects) Current or recent history of intolerance to or avoidance of dairy of at least one month duration (by self-report and self-reported symptoms). 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: • Currently pregnant 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 Recent use of systemic antibiotics defined as use within 30 days prior to screening Any of the following: Worked with metal (grinding, fabrication, etc.) or had an injury to the eye involving a metallic object (e.g., metallic slivers, foreign body, been injured by a metallic object that may NOT have been completely removed (e.g., bullets, shrapnel, BBs), had a reaction to a contrast medium used for MRI or CT, have claustrophobia (fear of closed places), been diagnosed with epilepsy/seizure, any reason you would be unable to remain still for long periods of time, Cardiac pacemaker, Any type of prosthesis (eye, penile), Implanted cardiac defibrillator, Heart valve prosthesis/stents, Aneurysm clip, Shunt (spinal/intraventricular), Neuro or Bone Stimulator, Wire sutures or surgical staples, Insulin or Infusion Pump, Bone/joint pin, screw, nail, plate, Implanted drug infusion device, Body tattoos, Cochlear, otologic or ear implant, Tattooed makeup (eyeliner, lip, etc.), Prostate radiation seeds, Breast tissue expander, IUD (intrauterine device), Hearing aids, Transdermal medicine patch (Nitro),Body piercing(s), Any metallic implants or objects, any other reason the participant thinks they would not be a good candidate for MRI. Any other conditions/issues noted by the study staff and/or Principal Investigator that would impact participation and/or protocol compliance

Sites / Locations

  • Purdue MRI Facility

Outcomes

Primary Outcome Measures

Volume of milk in stomach/gastric transit
Volume of milk in the stomach will be calculated using FSL software with MRI images acquired at 0, 10, 30, 60 and 120 minutes.

Secondary Outcome Measures

Difference in abdominal pain
Abdominal pain will be rated using a 6-point Likert Scale. The scale ranges from a score of 0 to 5 (0 = none, 1 =slight, 2 = mild, 3 = moderate, 4 = moderately severe, 5 = severe).

Full Information

First Posted
December 7, 2022
Last Updated
December 17, 2022
Sponsor
Purdue University
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1. Study Identification

Unique Protocol Identification Number
NCT05658861
Brief Title
Comparing the Gastric Transit of Commercial Milk and A2 Milk
Official Title
Comparing the Gastric Transit of Commercial Milk Containing A1 Beta-casein and A2 Milk Containing Only A2 Beta-casein Using Magnetic Resonance Imaging (MRI)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 21, 2021 (Actual)
Primary Completion Date
October 6, 2022 (Actual)
Study Completion Date
May 2023 (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. The μ-opioid peptide BCM-7 is released from A1 but not from A2. BCM-7 is associated with slower gastrointestinal transit and hence increased gastrointestinal transit times. Lactose maldigesters reported an increase in abdominal pain due to consumption of milk containing A1 beta-casein as compared to milk containing only A2 beta-casein. The hypothesis of this study is that the differential abdominal pain is due to the differential gastric transit. This is a double-blinded, randomized, controlled trial conducted to determine if the transit of A1 β-casein milk is modified in the stomach as compared to milk with only A2 β-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. Visit 1: Participants should fast for 12 hours and avoid consuming water for 3 hours prior to the MRI scanning appointment. On the day of the visit, participants will undergo a safety screening for MRI compatibility as required by the Purdue MRI Facility and Inner Vision West. Prior to MRI scanning, all participants will remove any metal objects and change into medical scrubs provided by the facility. Participants will then consume their first randomized milk containing 0.5 grams lactose per kilogram body weight (Upper limit - 0.5g/kg up to 50g of lactose). Images of the stomach will be obtained at 0 (pre dose/baseline), 10, 30, 60 and 120 minutes using a Magnetom 3T Prisma MRI scanner. Participants will rate their abdominal pain at 0, 30, 60, 90 and 120 minutes. 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, Adult Type

7. Study Design

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

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 commercial milk
Intervention Type
Other
Intervention Name(s)
Milk containing only A2 beta-casein
Other Intervention Name(s)
A2 milk
Intervention Description
Single dose of A2 milk
Primary Outcome Measure Information:
Title
Volume of milk in stomach/gastric transit
Description
Volume of milk in the stomach will be calculated using FSL software with MRI images acquired at 0, 10, 30, 60 and 120 minutes.
Time Frame
2 hours
Secondary Outcome Measure Information:
Title
Difference in abdominal pain
Description
Abdominal pain will be rated using a 6-point Likert Scale. 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
2 hours

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 Milk intolerant and identified as a lactose maldigester while participating in the Milk Protein Study (applicable only for subjects from the previous milk protein study and not applicable for new subjects) Current or recent history of intolerance to or avoidance of dairy of at least one month duration (by self-report and self-reported symptoms). 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: • Currently pregnant 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 Recent use of systemic antibiotics defined as use within 30 days prior to screening Any of the following: Worked with metal (grinding, fabrication, etc.) or had an injury to the eye involving a metallic object (e.g., metallic slivers, foreign body, been injured by a metallic object that may NOT have been completely removed (e.g., bullets, shrapnel, BBs), had a reaction to a contrast medium used for MRI or CT, have claustrophobia (fear of closed places), been diagnosed with epilepsy/seizure, any reason you would be unable to remain still for long periods of time, Cardiac pacemaker, Any type of prosthesis (eye, penile), Implanted cardiac defibrillator, Heart valve prosthesis/stents, Aneurysm clip, Shunt (spinal/intraventricular), Neuro or Bone Stimulator, Wire sutures or surgical staples, Insulin or Infusion Pump, Bone/joint pin, screw, nail, plate, Implanted drug infusion device, Body tattoos, Cochlear, otologic or ear implant, Tattooed makeup (eyeliner, lip, etc.), Prostate radiation seeds, Breast tissue expander, IUD (intrauterine device), Hearing aids, Transdermal medicine patch (Nitro),Body piercing(s), Any metallic implants or objects, any other reason the participant thinks they would not be a good candidate for MRI. Any other conditions/issues noted by the study staff and/or Principal Investigator that would impact participation and/or protocol compliance
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 MRI Facility
City
West Lafayette
State/Province
Indiana
ZIP/Postal Code
47907
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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

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Comparing the Gastric Transit of Commercial Milk and A2 Milk

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