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NCT Number: NCT06513026

Milk for Diabetes Prevention

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.

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Key information

Conditions

Lactose Intolerance Carbohydrate Metabolism, Inborn Errors Congenital, Hereditary, and Neonatal Diseases and Abnormalities Diabetes Mellitus Diabetes Mellitus, Type 2 Digestive System Diseases Endocrine System Diseases Gastrointestinal Diseases Genetic Diseases, Inborn Glucose Intolerance Glucose Metabolism Disorders Hyperglycemia Intestinal Diseases Lactase Persistence Lactose Intolerant Malabsorption Syndromes Metabolic Diseases Metabolism, Inborn Errors Nutritional and Metabolic Diseases Pre-diabetes

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

HCHS/SOL Bronx Field Center

The Bronx, New York, 10458, United States

Location status: Recruiting

Location contact

CONTACT

[email protected]

718-584-1563

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Lactose-Containing Milk

Dietary Supplement

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.

Lactose-Free Milk

Dietary Supplement

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.

Primary outcomes

  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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).

Study contacts

Contact information is provided by the study sponsor or research team.

Brandilyn Peters-Samuelson, PhD

CONTACT

[email protected]

718-430-3281

Qibin Qi, PhD

CONTACT

[email protected]

718-430-4203

Sponsors and collaborators

Lead sponsor

Albert Einstein College of Medicine

Other

Collaborators

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

Registry information

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Jul 22, 2024
Registry last updated
May 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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