Milk for Diabetes Prevention
NCT Number: NCT06513026
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Lactose Intolerance|Lactose Intolerant|Lactase Persistence|Pre-Diabetes|Diabetes Mellitus, Type 2
Interventions: DIETARY_SUPPLEMENT: Lactose-Containing Milk|DIETARY_SUPPLEMENT: Lactose-Free Milk
Sponsor: Albert Einstein College of Medicine
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2024-08
Completion Date: 2026-08
Locations: HCHS/SOL Bronx Field Center, Bronx, New York, 10458, United States

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.

Primary Outcome Measures: Gastrointestinal symptoms, Gastrointestinal symptoms, specifically abdominal pain, bloating, flatulence, and diarrhea, will be recorded daily 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 Baseline to Week 12|Change in Expired Breath Hydrogen, 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, 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, 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, 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, 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), 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, 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, 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, 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, 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, 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