Milk for Diabetes Prevention

May 21, 2026 updated by: Albert Einstein College of Medicine
Individuals with lactase non-persistence (LNP; determined by a functional variant in the LCT gene [rs4988235, GG genotype]) are susceptible to lactose intolerance in adulthood due to deficiency of lactase, the enzyme which digests milk lactose sugars. However, many LNP individuals still drink ≥1 cup of milk daily. Recent analysis in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) found that consumption of 1 serving (cup) of milk/day was associated with ~30% lower risk of type 2 diabetes among LNP individuals, but not among individuals with lactase persistence (LP). This beneficial effect might be partially explained by favorable alterations in gut microbiota and related metabolites associated with higher milk consumption among LNP individuals. Based on these observational study findings, the investigator team proposes to conduct a randomized, controlled trial of lactose-containing vs. lactose-free milk in LNP individuals with pre-diabetes, to comprehensively investigate the effects of milk intake on the gut microbiome and glycemic outcomes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The trial will feature a 2-week milk washout period, followed by 1:1 randomization to lactose-containing (1% or 2%) or lactose-free (1% or 2%) milk for 12 weeks (4 weeks each of ½ cup, 1 cup, and 2 cups milk). Before and after the 12 weeks, visits will entail lactose challenge hydrogen breath tests (HBT; i.e., lactose tolerance tests) and blood tests for fasting glucose, hemoglobin A1c, and metabolomics; while stool samples and continuous glucose monitoring (CGM) data will be collected at home using provided kits/devices.

Specific aims of the study are to: (1) establish feasibility and tolerability of a randomized trial of lactose-containing vs. lactose-free milk; (2) to examine the effect of lactose-containing milk on gut microbiome species, functions, and metabolites in LNP individuals with pre-diabetes; and (3) to examine the effect of lactose-containing milk on glycemic outcomes in LNP individuals with pre-diabetes.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • LNP genotype (LCT gene rs4988235, GG genotype)
  • History of pre-diabetes, defined as fasting blood glucose 100-125 mg/dL and/or hemoglobin A1c (HbA1c) 5.7-6.4% and have not been diagnosed with diabetes nor take diabetes medication (pre-diabetes determined at most recent study visit [for HCHS/SOL participant] or most recent medical chart or self-report [for other participant])
  • Drink ≤1 cup milk/day
  • Basic computer or smartphone skills
  • Can speak and read English fluently

Exclusion Criteria:

  • Diabetes diagnosis
  • Taking anti-diabetes medication
  • Cancer, cardiovascular disease (CVD), or life-threatening illness
  • Known milk allergy
  • Has severe GI symptoms after drinking milk
  • History of GI surgery
  • Had a double mastectomy
  • Smoking
  • More than 1 alcoholic beverage/day
  • Pregnant or breastfeeding
  • Colonoscopy in last 2 weeks
  • Antibiotics in last 3 months
  • Taking probiotics or fiber supplements (if taking, must be able to stop taking during study)
  • Taking laxatives, stool softeners, anti-diarrheal (if taking, must be able to stop taking during study)
  • Taking lactase pills (if taking, must be able to stop taking)
  • Participating in extreme dieting program
  • Planning extended travel that would prevent participation in study
  • Taking medication that must be taken separate from calcium or dairy products

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lactose-Containing Milk
Participants will be randomized to lactose-containing milk in strata of age (<60, ≥60) and sex (female, male). Within each age and sex stratum, 10 participants will be randomized into two intervention groups in a 1:1 ratio
Dietary supplement: Lactose-Containing Milk

Participants will be asked to drink regular milk (1% or 2%) for 12 weeks as follows:

  • Weeks 1-4: ½ cup milk per day
  • Weeks 5-8: 1 cup milk per day
  • Weeks 9-12: 2 cups milk per day

Participants will continue drinking 2 cups milk/day for 2 weeks after the 12-week follow-up visit.
Active Comparator: Lactose-Free Milk
Participants will be randomized to lactose-free milk in strata of age (<60, ≥60) and sex (female, male). Within each age and sex stratum, 10 participants will be randomized into two intervention groups in a 1:1 ratio
Dietary supplement: Lactose-Free Milk

Participants will be asked to drink 1% or 2% lactose-free milk for 12 weeks as follows:

  • Weeks 1-4: ½ cup milk per day
  • Weeks 5-8: 1 cup milk per day
  • Weeks 9-12: 2 cups milk per day

Participants will continue drinking 2 cups milk/day for 2 weeks after the 12-week follow-up visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Expired Breath Hydrogen
Time Frame: From Baseline to Week 12
Expired breath hydrogen after lactose challenge will be measured during the baseline visit and after 12 weeks of milk intervention at the time of the follow-up visit using Hydrogen Breath Test (HBT) kits. Breath tubes will be mailed to an external laboratory where stable isotope analysis for expired breath hydrogen will be conducted. Expired breath hydrogen will be expressed as incremental Area Under the Curve (iAUC). Change in iAUC from baseline to week 12 will be summarized using basic descriptive statistics (group means and standard deviations), and change in iAUC will be compared between treatment groups.
From Baseline to Week 12
Change in gut microbiome features - Relative Abundance of Species
Time Frame: From Baseline to Week 12
Stool samples will be collected using home stool microbiome kits at baseline, 4-, 8-, and 12-week timepoints. Shotgun sequencing will be conducted. Change in relative abundance of species (with >1% mean relative abundance) from baseline will summarized, using basic descriptive statistics (group means and standard deviations). Change in relative abundance of species from baseline will be compared between the treatment groups.
From Baseline to Week 12
Change in gut microbiome features - Functional Pathway Relative Abundance
Time Frame: From Baseline to Week 12
Stool samples will be collected using home stool microbiome kits at baseline, 4-, 8-, and 12-week timepoints. Shotgun sequencing will be conducted. Change in relative abundance of functional pathways (with >1% mean relative abundance) from baseline will summarized, using basic descriptive statistics (group means and standard deviations). Change in relative abundance of functional pathways from baseline will be compared between the treatment groups.
From Baseline to Week 12
Change in gut microbiome features - Metabolomics
Time Frame: From Baseline to Week 12
Targeted metabolic profiling will be performed on serum and stool samples (baseline and week 12) using LC-MS/MS methods for absolute quantitation of 70 metabolites associated with gut bacterial metabolism. Change in stool and serum metabolites from baseline will be summarized using basic descriptive statistics (group means and standard deviations). Change in stool and serum metabolites from baseline will be compared between the treatment groups.
From Baseline to Week 12
Change in glycemic outcomes - Fasting glucose
Time Frame: From Baseline to Week 12
Blood sera samples for fasting glucose will be collected at baseline and Week 12. Fasting glucose, i.e., blood sugar levels following an 8-hour fast, will be analyzed via standard analytical chemistry approaches and reported in mg/dL or mmol/L units. Ranges vary but a fasting glucose level <99 mg/dL is considered 'normal', between 100-125 mg/dL is within the 'pre-diabetic' range, >126 mg/dL is within the 'diabetic' range. Change in fasting glucose from baseline will be summarized using descriptive statistics (means and standard deviations) and compared between the treatment groups.
From Baseline to Week 12
Change in glycemic outcomes - Hemoglobin A1c (HbA1c)
Time Frame: From Baseline to Week 12
Whole blood samples for HbA1c will be collected at baseline and Week 12. HbA1c, used to measure the amount of hemoglobin with attached glucose and reflects average blood glucose levels over the past several months, will be analyzed via standard analytical chemistry approaches. Ranges vary, however, a 'normal' HbA1c is generally <5.7%, 5.7-6.4% is in the 'pre-diabetic' range and a value of 6.5% or greater is in the 'diabetic' range. Change in HbA1c from baseline will be summarized using descriptive statistics (means and standard deviations) and compared between the treatment groups.
From Baseline to Week 12
Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) mean glucose
Time Frame: From Screening visit to Week 14 visit
During screening visit participants will have a 2-week continuous glucose monitor (CGM) applied to the skin on the upper arm in advance of the 2-week milk washout period. The CGM will be returned during the baseline visit 2 weeks later. After the 12 week visit, another 2-week CGM will be applied during which time participants will continue drinking milk concurrent with the 2-week CGM (i.e., until 14 weeks). Change in mean glucose (mg/dL) from screening to week 14 will be summarized using descriptive statistics (means and standard deviations) and compared between the treatment groups.
From Screening visit to Week 14 visit
Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) glycemic variability
Time Frame: From Screening visit to Week 14 visit
During screening visit participants will have a 2-week continuous glucose monitor (CGM) applied to the skin on the upper arm in advance of the 2-week milk washout period. The CGM will be returned during the baseline visit 2 weeks later. After the 12 week visit, another 2-week CGM will be applied during which time participants will continue drinking milk concurrent with the 2-week CGM (i.e., until 14 weeks). Change in glycemic variability (%CV) from screening to week 14 will be summarized using descriptive statistics (means and standard deviations) and compared between the treatment groups.
From Screening visit to Week 14 visit
Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) time above range
Time Frame: From Screening visit to Week 14 visit
During screening visit participants will have a 2-week continuous glucose monitor (CGM) applied to the skin on the upper arm in advance of the 2-week milk washout period. The CGM will be returned during the baseline visit 2 weeks later. After the 12 week visit, another 2-week CGM will be applied during which time participants will continue drinking milk concurrent with the 2-week CGM (i.e., until 14 weeks). Change in time above range (%) from screening to week 14 will be summarized using descriptive statistics (means and standard deviations) and compared between the treatment groups.
From Screening visit to Week 14 visit
Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) time in range
Time Frame: From Screening visit to Week 14 visit
During screening visit participants will have a 2-week continuous glucose monitor (CGM) applied to the skin on the upper arm in advance of the 2-week milk washout period. The CGM will be returned during the baseline visit 2 weeks later. After the 12 week visit, another 2-week CGM will be applied during which time participants will continue drinking milk concurrent with the 2-week CGM (i.e., until 14 weeks). Change in time in range (%) from screening to week 14 will be summarized using descriptive statistics (means and standard deviations) and compared between the treatment groups.
From Screening visit to Week 14 visit
Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) time below range
Time Frame: From Screening visit to Week 14 visit
During screening visit participants will have a 2-week continuous glucose monitor (CGM) applied to the skin on the upper arm in advance of the 2-week milk washout period. The CGM will be returned during the baseline visit 2 weeks later. After the 12 week visit, another 2-week CGM will be applied during which time participants will continue drinking milk concurrent with the 2-week CGM (i.e., until 14 weeks). Change in time below range (%) from screening to week 14 will be summarized using descriptive statistics (means and standard deviations) and compared between the treatment groups.
From Screening visit to Week 14 visit
Gastrointestinal symptoms
Time Frame: Daily From Screening visit to Week 12
Gastrointestinal symptoms, specifically abdominal pain, bloating, flatulence, and diarrhea, will be recorded daily from screening visit through 12 weeks of milk intervention. The occurrence and severity of these four adverse events will be summarized and reported by study arm. Average frequencies of none-mild vs. moderate-severe symptoms will be compared between treatment groups by week of study, as well as for specific time intervals corresponding to milk doses (weeks 1-4, 5-8, 9-12).
Daily From Screening visit to Week 12
Change in Flatulence
Time Frame: From Screening to Week 1, from Week 1 to Week 10, and from Week 1 to Week 14
The Smart Underwear device will be worn externally on regular underwear near the rectum/perineum during specified daytime wear periods. The device continuously detects hydrogen in expelled flatus and records supporting temperature and movement data. These data will be used to derive the frequency of flatus events per wear period, which reflects intestinal gas production and gut microbial activity. De-identified data will be transferred after each wear period through the Human Flatus Atlas mobile app and uploaded to servers. Change in frequency of flatus events per wear period will be summarized using basic descriptive statistics (group means and standard deviations).
From Screening to Week 1, from Week 1 to Week 10, and from Week 1 to Week 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Albert Einstein College of Medicine

Collaborators

National Dairy Council
Metabolic Solutions Inc.
University of Minnesota (UM) Advanced Research and Diagnostic Laboratory (ARDL)
Azenta Life Sciences

Investigators

  • Principal Investigator: Brandilyn Peters-Samuelson, PhD, Albert Einstein College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2026

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

July 16, 2024

First Submitted That Met QC Criteria

July 19, 2024

First Posted (Actual)

July 22, 2024

Study Record Updates

Last Update Posted (Actual)

May 26, 2026

Last Update Submitted That Met QC Criteria

May 21, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-16045

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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