Dairy IntoleranceNCT03713346
Comparing the Digestion of Milk With Different Beta-casein Protein Content by Dairy Intolerant Persons
A study testing Lactose free milk, Jersey milk and High A1 β-casein milk in people with Dairy Intolerance, run by Purdue University at 1 site in United States.
Trial summary
Persons with dairy intolerance may experience cramps/abdominal pain, bloating, flatulence, acute diarrhea, or fecal urgency when they ingest excessive amounts of lactose. The intensity of these conditions can be mild or severe and likely depends on numerous variables including dose, transit time, intestinal residual… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Dairy Intolerance
- What is being tested?
- Lactose free milk, Jersey milk and High A1 β-casein milk
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jan 2018to 3 Sep 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability/desire to provide informed consent
- Aged 18 to 65 years of age inclusive at screening
- Current or recent history of intolerance to and avoidance of milk of at least one month duration (by self-report and self-reported symptoms).
- Agrees to refrain from all other treatments and products used for lactose intolerance (e.g., Lactaid® Dietary Supplements) during study involvement
- Willing to return for all study visits and complete all study related procedures, including fasting before and during the hydrogen breath tests
- Qualifying Lactose Challenge Symptom Score:
Show all 10Show fewer
- (4 symptom categories with severity measured on from 0 to 5) as defined by one of the following:
- At least one score of "moderately severe" or "severe" on a single symptom during the 6 hour HBT test;
- A score of "moderate" or greater for a single symptom on at least two (2) time points during the 6 hour HBT test;
- At least one "moderate" score or greater on each of two symptoms during the 6 hour HBT test 7. Hydrogen concentration of at least 20 parts per million greater than baseline at least 2 time points during the screening hydrogren breath test 8. Able to understand and provide written informed consent in English
Who cannot join
- 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]
Show all 24Show fewer
- 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
- 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 lactose 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 lactose 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
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Purdue University
West Lafayette, Indiana, 47907-2059
About this study
Persons with dairy intolerance may experience cramps/abdominal pain, bloating, flatulence, acute diarrhea, or fecal urgency when they ingest excessive amounts of lactose. The intensity of these conditions can be mild or severe and likely depends on numerous variables including dose, transit time, intestinal residual lactase activity and microbiome potential to ferment lactose. Jersey cattle produce milk containing high levels of the A2 β-casein protein . There are claims that high A2 β-casein milk is more easily digested by people who are lactose maldigesters . We propose to conduct a double-blinded, randomized, controlled trial to determine if high A2 β-casein milk from Jersey cattle is actually better digested and tolerated by lactose maldigesters.
Read the detailed description
Persons with dairy intolerance may experience cramps/abdominal pain, bloating, flatulence, acute diarrhea, or fecal urgency when they ingest excessive amounts of lactose. The intensity of these conditions can be mild or severe and likely depends on numerous variables including dose, transit time, intestinal residual lactase activity and microbiome potential to ferment lactose. Jersey cattle produce milk containing high levels of the A2 β-casein protein . There are claims that high A2 β-casein milk is more easily digested by people who are lactose maldigesters . We propose to conduct a double-blinded, randomized, controlled trial to determine if high A2 β-casein milk from Jersey cattle is actually better digested and tolerated by lactose maldigesters.
This proposed protocol comparing the dairy intolerance symptoms from milks containing predominantly the A1 variant versus A2 variant will establish if high A2 milk is better digested and/or tolerated than high A1 milk.
Participants will be asked to consume four different commercially available milks in random order. The samples will be fed for breakfast separated by at least 10 days, after overnight fasts. The commercial milk treatments will include; high A1 β-casein milk (commercial milk), high A2 β-casein milk, Jersey cattle milk (which contains a mixture of A1 and A2 β-casein), and a lactose free milk control. Milk will be 2% fat content to control for transit. Each subject will be fed milk containing 0.5g lactose per kg body weight. There will be two arms in this study: dairy intolerant who are lactose maldigesters, and dairy intolerant who are lactose digesters.
- Conditions
- Dairy Intolerance
- Being tested
- Lactose free milk, Jersey milk, High A1 β-casein milk, High A2 β-casein milk
- Keywords
- lactose, dairy, intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactose free milkOther
Single dose of lactose free milk
Jersey milkOther
Single dose of jersey milk
High A1 β-casein milkOther
Single dose of high A1 β-casein milk (commercial milk)
High A2 β-casein milkOther
Single dose of A2 β-casein milk
| Study group | Role | What they receive |
|---|---|---|
| Lactose digester | Other | Not described Receives: Other: Lactose free milk; Other: Jersey milk; Other: High A1 β-casein milk; Other: High A2 β-casein milk |
| Lactose maldigester | Other | Not described Receives: Other: Lactose free milk; Other: Jersey milk; Other: High A1 β-casein milk; Other: High A2 β-casein milk |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in AUC ΔH2 concentrations
Differences in AUC ΔH2 concentrations (primary outcomes) among milk phases is examined by repeated-measures analysis of variance (ANOVA)
Measured: Within the 6 hours following the milk challenge
Secondary outcomes (1)
Differences within each of the symptom categories
Repeated-measures ANOVA is also used to test for differences within each of the symptom categories (secondary outcomes) after transforming to correct for nonstationary variance. For both the H2 concentrations and symptom levels, to be able to detect differences between every single treatment, pairwise differences are examined using least significant difference (LSD).
Measured: Within the 6 hours following the milk challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2018
- Study start17 Jan 2018
- Primary completion3 Sep 2021
- Study completion3 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (46)Papers the sponsor has linked to this study.
- Other trials for Dairy IntoleranceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Purdue University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dennis A. Savaiano, Purdue University
- Investigators
- Dennis A Savaiano, PhD, Principal investigator, Purdue University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03713346
- Sponsor's protocol ID
- 1710019781
- Status last verified
- Oct 2021
- First submitted
- 4 Apr 2018
- Last updated
- 8 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Briet F, Pochart P, Marteau P, Flourie B, Arrigoni E, Rambaud JC. Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect? Gut. 1997 Nov;41(5):632-5. doi: 10.1136/gut.41.5.632.
PubMed 9414969Dairy Farmer. (2011). Specialist A2 milk venture. Cengage Learning, Inc. 2.
Brown-Esters, O., Mc Namara, P., & Savaiano, D. (2012). Dietary and biological factors influencing lactose intolerance. International Dairy Journal, 22(2), 98-103.
Davies, D.T. & Law, A.J.R. (1980). The content and composition of creamery milks in south-west Scotland. J Dairy Res, 47, 80-90.
Carroccio A, Montalto G, Cavera G, Notarbatolo A. Lactose intolerance and self-reported milk intolerance: relationship with lactose maldigestion and nutrient intake. Lactase Deficiency Study Group. J Am Coll Nutr. 1998 Dec;17(6):631-6. doi: 10.1080/07315724.1998.10718813.
PubMed 9853544de Silva P, Rachman S. Human food aversions: nature and acquisition. Behav Res Ther. 1987;25(6):457-68. doi: 10.1016/0005-7967(87)90053-2. No abstract available.
PubMed 3426508Dehkordi N, Rao DR, Warren AP, Chawan CB. Lactose malabsorption as influenced by chocolate milk, skim milk, sucrose, whole milk, and lactic cultures. J Am Diet Assoc. 1995 Apr;95(4):484-6. doi: 10.1016/S0002-8223(95)00126-3. No abstract available.
PubMed 7699193DOELL RG, KRETCHMER N. Studies of small intestine during development. I. Distribution and activity of beta-galactosidase. Biochim Biophys Acta. 1962 Aug 13;62:353-62. doi: 10.1016/0006-3002(62)90097-5. No abstract available.
PubMed 13886893Gilliland SE, Kim HS. Effect of viable starter culture bacteria in yogurt on lactose utilization in humans. J Dairy Sci. 1984 Jan;67(1):1-6. doi: 10.3168/jds.S0022-0302(84)81260-6.
PubMed 6707296Gustavsson F, Buitenhuis AJ, Johansson M, Bertelsen HP, Glantz M, Poulsen NA, Lindmark Mansson H, Stalhammar H, Larsen LB, Bendixen C, Paulsson M, Andren A. Effects of breed and casein genetic variants on protein profile in milk from Swedish Red, Danish Holstein, and Danish Jersey cows. J Dairy Sci. 2014;97(6):3866-77. doi: 10.3168/jds.2013-7312. Epub 2014 Apr 3.
PubMed 24704225Haverberg L, Kwon PH, Scrimshaw NS. Comparative tolerance of adolescents of differing ethic backgrounds to lactose-containing and lactose-free dairy drinks. I. Initial experience with a double-blind procedure. Am J Clin Nutr. 1980 Jan;33(1):17-21. doi: 10.1093/ajcn/33.1.17.
PubMed 7188826Hayes, J. (2014). Farm Weekly. A2 milk drinkers may get less gut aches. Global Reference on the Environment, Energy, and Natural Resources.
He T, Priebe MG, Harmsen HJ, Stellaard F, Sun X, Welling GW, Vonk RJ. Colonic fermentation may play a role in lactose intolerance in humans. J Nutr. 2006 Jan;136(1):58-63. doi: 10.1093/jn/136.1.58.
PubMed 16365059Hertzler SR, Savaiano DA. Colonic adaptation to daily lactose feeding in lactose maldigesters reduces lactose intolerance. Am J Clin Nutr. 1996 Aug;64(2):232-6. doi: 10.1093/ajcn/64.2.232.
PubMed 8694025Ho S, Woodford K, Kukuljan S, Pal S. Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study. Eur J Clin Nutr. 2014 Sep;68(9):994-1000. doi: 10.1038/ejcn.2014.127. Epub 2014 Jul 2.
PubMed 24986816
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing the Digestion of Milk With Different Beta-casein Protein Content by Dairy Intolerant Persons
- ClinicalTrials.gov ID
- NCT03713346
- Acronym / sponsor ID
- 1710019781
- Conditions
- Dairy Intolerance
- Keywords
- lactose, dairy, intolerance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Purdue UniversityUniversity, hospital or other
- Study start
- 17 Jan 2018 (actual)
- Primary completion
- 3 Sep 2021 (actual)
- Study completion
- 3 Sep 2021 (actual)
- First posted
- 19 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Persons with dairy intolerance may experience cramps/abdominal pain, bloating, flatulence, acute diarrhea, or fecal urgency when they ingest excessive amounts of lactose. The intensity of these conditions can be mild or severe and likely depends on numerous variables including dose, transit time, intestinal residual lactase activity and microbiome potential to ferment lactose. Jersey cattle produce milk containing high levels of the A2 β-casein protein . There are claims that high A2 β-casein milk is more easily digested by people who are lactose maldigesters . We propose to conduct a double-blinded, randomized, controlled trial to determine if high A2 β-casein milk from Jersey cattle is actually better digested and tolerated by lactose maldigesters.
Detailed description
Persons with dairy intolerance may experience cramps/abdominal pain, bloating, flatulence, acute diarrhea, or fecal urgency when they ingest excessive amounts of lactose. The intensity of these conditions can be mild or severe and likely depends on numerous variables including dose, transit time, intestinal residual lactase activity and microbiome potential to ferment lactose. Jersey cattle produce milk containing high levels of the A2 β-casein protein . There are claims that high A2 β-casein milk is more easily digested by people who are lactose maldigesters . We propose to conduct a double-blinded, randomized, controlled trial to determine if high A2 β-casein milk from Jersey cattle is actually better digested and tolerated by lactose maldigesters.
This proposed protocol comparing the dairy intolerance symptoms from milks containing predominantly the A1 variant versus A2 variant will establish if high A2 milk is better digested and/or tolerated than high A1 milk.
Participants will be asked to consume four different commercially available milks in random order. The samples will be fed for breakfast separated by at least 10 days, after overnight fasts. The commercial milk treatments will include; high A1 β-casein milk (commercial milk), high A2 β-casein milk, Jersey cattle milk (which contains a mixture of A1 and A2 β-casein), and a lactose free milk control. Milk will be 2% fat content to control for transit. Each subject will be fed milk containing 0.5g lactose per kg body weight. There will be two arms in this study: dairy intolerant who are lactose maldigesters, and dairy intolerant who are lactose digesters.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lactose digester | Other | Other: Lactose free milk, Other: Jersey milk, Other: High A1 β-casein milk, Other: High A2 β-casein milk |
| Lactose maldigester | Other | Other: Lactose free milk, Other: Jersey milk, Other: High A1 β-casein milk, Other: High A2 β-casein milk |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Ability/desire to provide informed consent
- Aged 18 to 65 years of age inclusive at screening
- Current or recent history of intolerance to and avoidance of milk of at least one month duration (by self-report and self-reported symptoms).
- Agrees to refrain from all other treatments and products used for lactose intolerance (e.g., Lactaid® Dietary Supplements) during study involvement
- Willing to return for all study visits and complete all study related procedures, including fasting before and during the hydrogen breath tests
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lactose free milkSingle dose of lactose free milk | Other | Lactose digester, Lactose maldigester |
| Jersey milkSingle dose of jersey milk | Other | Lactose digester, Lactose maldigester |
| High A1 β-casein milkSingle dose of high A1 β-casein milk (commercial milk) | Other | Lactose digester, Lactose maldigester |
| High A2 β-casein milkSingle dose of A2 β-casein milk | Other | Lactose digester, Lactose maldigester |
Primary outcome
Differences in AUC ΔH2 concentrations
Time frame: Within the 6 hours following the milk challenge
Differences in AUC ΔH2 concentrations (primary outcomes) among milk phases is examined by repeated-measures analysis of variance (ANOVA)
1 secondary outcome
Differences within each of the symptom categories
Time frame: Within the 6 hours following the milk challenge
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Background: PubMed 9414969Briet F, Pochart P, Marteau P, Flourie B, Arrigoni E, Rambaud JC. Improved clinical tolerance to chronic lactose ingestion in subjects with lactose intolerance: a placebo effect? Gut. 1997 Nov;41(5):632-5. doi: 10.1136/gut.41.5.632.
- BackgroundDairy Farmer. (2011). Specialist A2 milk venture. Cengage Learning, Inc. 2.
- BackgroundBrown-Esters, O., Mc Namara, P., & Savaiano, D. (2012). Dietary and biological factors influencing lactose intolerance. International Dairy Journal, 22(2), 98-103.
- BackgroundDavies, D.T. & Law, A.J.R. (1980). The content and composition of creamery milks in south-west Scotland. J Dairy Res, 47, 80-90.
- Background: PubMed 9853544Carroccio A, Montalto G, Cavera G, Notarbatolo A. Lactose intolerance and self-reported milk intolerance: relationship with lactose maldigestion and nutrient intake. Lactase Deficiency Study Group. J Am Coll Nutr. 1998 Dec;17(6):631-6. doi: 10.1080/07315724.1998.10718813.
- Background: PubMed 3426508de Silva P, Rachman S. Human food aversions: nature and acquisition. Behav Res Ther. 1987;25(6):457-68. doi: 10.1016/0005-7967(87)90053-2. No abstract available.
- Background: PubMed 7699193Dehkordi N, Rao DR, Warren AP, Chawan CB. Lactose malabsorption as influenced by chocolate milk, skim milk, sucrose, whole milk, and lactic cultures. J Am Diet Assoc. 1995 Apr;95(4):484-6. doi: 10.1016/S0002-8223(95)00126-3. No abstract available.
- Background: PubMed 13886893DOELL RG, KRETCHMER N. Studies of small intestine during development. I. Distribution and activity of beta-galactosidase. Biochim Biophys Acta. 1962 Aug 13;62:353-62. doi: 10.1016/0006-3002(62)90097-5. No abstract available.
- Background: PubMed 6707296Gilliland SE, Kim HS. Effect of viable starter culture bacteria in yogurt on lactose utilization in humans. J Dairy Sci. 1984 Jan;67(1):1-6. doi: 10.3168/jds.S0022-0302(84)81260-6.
- Background: PubMed 24704225Gustavsson F, Buitenhuis AJ, Johansson M, Bertelsen HP, Glantz M, Poulsen NA, Lindmark Mansson H, Stalhammar H, Larsen LB, Bendixen C, Paulsson M, Andren A. Effects of breed and casein genetic variants on protein profile in milk from Swedish Red, Danish Holstein, and Danish Jersey cows. J Dairy Sci. 2014;97(6):3866-77. doi: 10.3168/jds.2013-7312. Epub 2014 Apr 3.
- Background: PubMed 7188826Haverberg L, Kwon PH, Scrimshaw NS. Comparative tolerance of adolescents of differing ethic backgrounds to lactose-containing and lactose-free dairy drinks. I. Initial experience with a double-blind procedure. Am J Clin Nutr. 1980 Jan;33(1):17-21. doi: 10.1093/ajcn/33.1.17.
- BackgroundHayes, J. (2014). Farm Weekly. A2 milk drinkers may get less gut aches. Global Reference on the Environment, Energy, and Natural Resources.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dennis A Savaiano, PhD principal investigator
Purdue University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lactose free milk, Jersey milk and High A1 β-casein milk in people with Dairy Intolerance, run by Purdue University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in AUC ΔH2 concentrations (time frame: Within the 6 hours following the milk challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03713346, which also lists 46 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021.