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A1-Free vs. Conventional Milk Metabolic Response Study

A Randomized Crossover Study Evaluating Postprandial Glucose and Insulin Responses to A1-Free and Conventional Milk With and Without a Delayed Lactose Challenge in Healthy Adults

Status
Not yet recruiting
Phases
Unknown
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT07567443
Enrollment
35
Registered
2026-05-05
Start date
2026-06-15
Completion date
2027-01-31
Last updated
2026-05-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Insulin Response, Lactose Digestion, Postprandial Glucose Response, Postprandial Metabolism

Keywords

A1 beta-casein, A1-free milk, Postprandial glucose, Insulin response, Postprandial Glycemia, Digestive Kinetics, Lactose digestion, Metabolic response

Brief summary

This study will examine how different types of milk affect blood sugar and insulin responses after eating. Specifically, the study compares milk that contains only A2 beta-casein protein (A1-free milk) to conventional milk, which contains both A1 and A2 proteins. Participants will complete four study visits in which they will consume different milk-based beverages. These include lactose-containing milk and lactose-free milk followed by a lactose drink given later. Blood samples will be collected over several hours to measure glucose and insulin responses. Breath tests and questionnaires will also be used to assess digestion and gastrointestinal symptoms. The goal of this study is to determine whether milk protein type influences metabolic responses and whether consuming lactose-free milk affects how the body processes lactose when it is consumed later.

Detailed description

Postprandial glucose and insulin responses are important indicators of metabolic health, even in individuals without diagnosed metabolic disease. The rate and pattern of nutrient digestion and absorption can influence these responses, and emerging evidence suggests that differences in milk protein composition, specifically the presence or absence of A1 beta-casein, may alter gastrointestinal function and metabolic outcomes. This study is a randomized, double-blind, crossover trial designed to evaluate the effects of A1-free milk compared to conventional milk on postprandial metabolic responses in healthy adults. Participants will complete four experimental conditions in random order: (1) lactose-containing A1-free milk, (2) lactose-containing conventional milk, (3) lactose-free A1-free milk followed by a delayed lactose challenge, and (4) lactose-free conventional milk followed by a delayed lactose challenge. The inclusion of both lactose-containing and lactose-free conditions allows for evaluation of two complementary questions. First, direct comparisons between lactose-containing A1-free and conventional milk will assess whether milk protein composition influences postprandial glucose and insulin responses under typical consumption conditions. Second, the lactose-free preload conditions, combined with a standardized delayed lactose challenge, are designed to evaluate whether prior milk consumption modifies subsequent metabolic responses to lactose exposure. This approach provides insight into potential differences in digestive kinetics, including gastric emptying, nutrient delivery, and lactose digestion and absorption. During each study visit, participants will consume a standardized milk-based intervention following an overnight fast. In the lactose-free conditions, a lactose beverage matched to the amount of lactose typically present in the milk will be administered 60 minutes after milk consumption. Blood samples will be collected at multiple timepoints over a postprandial period to measure glucose and insulin concentrations and characterize response patterns, including early-phase responses and overall exposure. Secondary and exploratory outcomes include breath hydrogen testing as a non-invasive marker of carbohydrate fermentation and lactose maldigestion, as well as gastrointestinal symptom assessments using validated questionnaires. These measures will be used to provide additional context for interpreting metabolic responses across conditions. The crossover design allows each participant to serve as their own control, improving statistical power and reducing variability. The findings from this study will help clarify whether differences in milk protein composition influence metabolic responses and whether prior exposure to lactose-free milk alters the body's handling of lactose consumed at a later time.

Interventions

DIETARY_SUPPLEMENTLactose-Containing A1-Free Milk

A lactose-containing milk beverage containing A2 beta-casein and no A1 beta-casein, consumed during one experimental study visit.

DIETARY_SUPPLEMENTLactose-Containing Conventional Milk

A lactose-containing conventional milk beverage containing both A1 and A2 beta-casein, consumed during one experimental study visit.

DIETARY_SUPPLEMENTLactose-Free A1-Free Milk With Delayed Lactose Drink

A lactose-free A1-free milk beverage consumed at the start of the study visit, followed by a lactose drink administered 60 minutes after milk consumption. The lactose drink is matched to the amount of lactose expected in the milk serving.

DIETARY_SUPPLEMENTLactose-Free Conventional Milk With Delayed Lactose Drink

A lactose-free conventional milk beverage containing both A1 and A2 beta-casein consumed at the start of the study visit, followed by a lactose drink administered 60 minutes after milk consumption. The lactose drink is matched to the amount of lactose expected in the milk serving.

Sponsors

Purdue University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes

Inclusion criteria

* Ability/desire to provide informed consent * Are between 18 and 65 years of age * Are generally healthy, with no known metabolic or gastrointestinal conditions that would affect digestion or metabolism * Are willing to consume milk-based beverages and lactose-containing drinks as part of the study * Are willing to fast overnight (approximately 10-12 hours) prior to study visits and follow study instructions (e.g., diet and activity restrictions) * Are willing to attend all study visits and complete all study procedures (blood draws, breath tests, urine samples, questionnaires) * Are able to understand and provide written informed consent in English.

Exclusion criteria

* You have a known allergy to milk or dairy products * You are currently pregnant, planning to become pregnant, or breastfeeding * You currently smoke or have used tobacco or nicotine-containing products within the past 3 months * You have a history of excessive alcohol use within the past 30 days * You have been diagnosed with diabetes (Type 1 or Type 2), prediabetes, or other metabolic conditions that affect glucose or insulin responses (such as insulin resistance, metabolic syndrome, or polycystic ovary syndrome \[PCOS\]) * You have a history of gastrointestinal conditions that may affect digestion or absorption (such as inflammatory bowel disease, Crohn's disease, ulcerative colitis, celiac disease, or severe irritable bowel syndrome) * You have had gastrointestinal surgery that alters normal digestive function (such as bariatric surgery or gastric bypass) * You have other medical conditions that may affect digestion or interfere with study results (such as 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.) * You have used medications or supplements known to affect glucose metabolism, digestion, or gastrointestinal function within the following timeframes prior to enrollment: * Within 4 weeks: insulin, metformin, GLP-1 receptor agonists, corticosteroids, digestive enzymes, fiber supplements, and all oral or IV antibiotics * Within 2 weeks: bismuth-containing compounds (e.g., Pepto-Bismol) and proton pump inhibitors or acid suppressors (e.g., omeprazole \[Prilosec\], lansoprazole \[Prevacid\], esomeprazole \[Nexium\], pantoprazole \[Protonix\], rabeprazole \[Aciphex\]) * Within 1 week: laxatives and stool softeners (e.g., Miralax, Colace, senna, lactulose, Citrucel, Metamucil, Fibercon), probiotics and prebiotics, gastrointestinal motility agents (e.g., Reglan, Linzess, Amitiza), and antidiarrheal medications (e.g., loperamide \[Imodium\], Lomotil) * You have had a recent infection within the past 30 days * You have been diagnosed with Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C * You are currently undergoing chemotherapy * Height: \_\_\_ Weight: \_\_\_ BMI: \_\_\_ Weighing \<16.5 kg or Body mass index \> 35 kg/m2 * You have participated in another clinical trial or used an investigational product within the past 30 days * You have any other condition that, as determined by the study team, would make participation unsafe or interfere with study results

Design outcomes

Primary

MeasureTime frameDescription
Postprandial Plasma Insulin Incremental Area Under the Curve (iAUC)0 to 180 minutes post-intervention during each study visitIncremental area under the curve (iAUC) for plasma insulin concentrations following consumption of each study condition, measured from serial blood samples collected via an indwelling catheter.
Postprandial Plasma Glucose Incremental Area Under the Curve (iAUC)0 to 180 minutes post-intervention during each study visitIncremental area under the curve (iAUC) for plasma glucose concentrations following consumption of each study condition, measured from serial blood samples collected via an indwelling catheter.

Secondary

MeasureTime frameDescription
Early-Phase Postprandial Glucose and Insulin Response0 to 60 minutes post-interventionEarly-phase postprandial response assessed by incremental area under the curve (iAUC) for plasma glucose and insulin concentrations.
Time to Peak Plasma Glucose and Insulin Concentrations (Tmax)0 to 180 minutes post-interventionTime required to reach peak plasma glucose and insulin concentrations following each study condition.
Circulating Metabolite Responses0, 30, 60, and 120 minutesPostprandial changes in circulating metabolites, including amino acids and acylcarnitines, measured from plasma samples to assess metabolic responses.
Breath Hydrogen ConcentrationsBaseline and every 30 minutes from 0 to 180 minutes post-interventionBreath hydrogen levels measured as a non-invasive marker of carbohydrate fermentation and lactose maldigestion.
Gastrointestinal Symptom ScoresBaseline and at 60, 120, and 180 minutes post-interventionSelf-reported gastrointestinal symptoms (e.g., bloating, gas, abdominal discomfort) assessed using visual analog scale and Likert-type questionnaires.
Urinary Galactose ConcentrationsBaseline and 180 minutes post interventionUrinary galactose concentrations measured as an marker of lactose metabolism.

Contacts

CONTACTLaura A Robinson, PhD
ldelvers@purud.edu908-442-3688
PRINCIPAL_INVESTIGATORDennis A Savaiano, PhD

Purdue University

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: May 6, 2026