Clinical trial NCT06513026: Milk for Diabetes Prevention
Official title: Milk for Diabetes Prevention
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Lactose Intolerance
Lactose Intolerant
Lactase Persistence
Pre-Diabetes
Diabetes Mellitus, Type 2
Keywords: Lactose
Lactose-free
Lactase Non Persistence
Lead sponsor: Albert Einstein College of Medicine
Sponsor class: OTHER
Collaborators: name: National Dairy Council
First posted: 2024-07-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: The trial will feature a 2-week milk washout period, followed by 1:1 randomization to lactose-containing or lactose-free 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.

Eligibility criteria: Inclusion Criteria:

* Age ≥18
* 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. If blood test over 3 years ago, pre-diabetes will be confirmed using finger-stick HbA1c.
* Drink ≤1 cup milk/day
* Basic computer or smartphone skills
* English or Spanish speaking

Exclusion Criteria:

* Diabetes diagnosis
* Taking anti-diabetes medication
* Blood test with history of pre-diabetes conducted \>3 years ago and finger-stick HbA1c is normal (≤5.6%).
* Cancer, cardiovascular disease (CVD), or life-threatening illness
* Known milk allergy
* Has severe GI symptoms after drinking milk
* History of GI surgery
* Smoking
* ≤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-diarrheals (if taking, must be able to stop taking during study)
* Participating in any extreme dieting programs

Primary outcomes:
measure: Gastrointestinal symptoms
timeFrame: Daily From Screening visit to Week 12
measure: Change in Expired Breath Hydrogen
timeFrame: From Baseline to Week 12
measure: Change in gut microbiome features - Relative Abundance of Species
timeFrame: From Baseline to Week 12
measure: Change in gut microbiome features - Functional Pathway Relative Abundance
timeFrame: From Baseline to Week 12
measure: Change in gut microbiome features - Metabolomics
timeFrame: From Baseline to Week 12
measure: Change in glycemic outcomes - Fasting glucose
timeFrame: From Baseline to Week 12
measure: Change in glycemic outcomes - Hemoglobin A1c (HbA1c)
timeFrame: From Baseline to Week 12
measure: Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) mean glucose
timeFrame: From Screening visit to Week 14 visit
measure: Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) glycemic variability
timeFrame: From Screening visit to Week 14 visit
measure: Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) time above range
timeFrame: From Screening visit to Week 14 visit
measure: Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) time in range
timeFrame: From Screening visit to Week 14 visit
measure: Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) time below range
timeFrame: From Screening visit to Week 14 visit
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: HCHS/SOL Bronx Field Center
state: New York
Study officials:
affiliation: Albert Einstein College of Medicine
name: Brandilyn Peters-Samuelson, PhD
role: PRINCIPAL_INVESTIGATOR
References: