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.
Brief Title
Milk for Diabetes Prevention
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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
718-430-3281
Central Contact Email
brandilyn.peterssamuelson@einsteinmed.edu
Central Contact Role
Contact
Central Contact Phone
718-430-4203
Central Contact Email
qibin.qi@einsteinmed.edu
Completion Date
Completion Date Type
Estimated
Conditions
LACTOSE INTOLERANCE
LACTOSE INTOLERANT
LACTASE PERSISTENCE
PRE-DIABETES
DIABETES MELLITUS, TYPE 2
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
Lactose
Lactose-free
Lactase Non Persistence
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
70 Years
Minimum Age
18 Years
NCT Id
NCT06513026
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2024-16045
Overall Status
Recruiting
Phases
Not Applicable
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Milk for Diabetes Prevention
Primary Outcomes
Outcome Description
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).
Outcome Measure
Gastrointestinal symptoms
Outcome Time Frame
Daily From Screening visit to Week 12
Outcome Description
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.
Outcome Measure
Change in Expired Breath Hydrogen
Outcome Time Frame
From Baseline to Week 12
Outcome Description
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.
Outcome Measure
Change in gut microbiome features - Relative Abundance of Species
Outcome Time Frame
From Baseline to Week 12
Outcome Description
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.
Outcome Measure
Change in gut microbiome features - Functional Pathway Relative Abundance
Outcome Time Frame
From Baseline to Week 12
Outcome Description
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.
Outcome Measure
Change in gut microbiome features - Metabolomics
Outcome Time Frame
From Baseline to Week 12
Outcome Description
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.
Outcome Measure
Change in glycemic outcomes - Fasting glucose
Outcome Time Frame
From Baseline to Week 12
Outcome Description
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.
Outcome Measure
Change in glycemic outcomes - Hemoglobin A1c (HbA1c)
Outcome Time Frame
From Baseline to Week 12
Outcome Description
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.
Outcome Measure
Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) mean glucose
Outcome Time Frame
From Screening visit to Week 14 visit
Outcome Description
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.
Outcome Measure
Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) glycemic variability
Outcome Time Frame
From Screening visit to Week 14 visit
Outcome Description
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.
Outcome Measure
Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) time above range
Outcome Time Frame
From Screening visit to Week 14 visit
Outcome Description
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.
Outcome Measure
Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) time in range
Outcome Time Frame
From Screening visit to Week 14 visit
Outcome Description
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.
Outcome Measure
Change in glycemic outcomes - Continuous Glucose Monitoring (CGM) time below range
Outcome Time Frame
From Screening visit to Week 14 visit
Outcome Description
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).
Outcome Measure
Change in Flatulence
Outcome Time Frame
From Screening to Week 1, from Week 1 to Week 10, and from Week 1 to Week 14
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
70
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Brandilyn Peters-Samuelson
Investigator Email
brandilyn.peterssamuelson@einsteinmed.edu
Investigator Department
Epidemiology & Population Health
Investigator Division
Epidemiology
Investigator Sponsor Organization
External
Study Department
Epidemiology and Population Health
Study Division
Epidemiology
Categories Mesh Debug
Diabetes & Endocrine System --- DIABETES MELLITUS, TYPE 2
Digestive System --- INTESTINAL DISEASES
Digestive System --- GASTROINTESTINAL DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Diabetes --- METABOLIC DISEASES
Diabetes & Endocrine System --- METABOLIC DISEASES
Diabetes & Endocrine System --- HYPERGLYCEMIA
Diabetes --- GLUCOSE METABOLISM DISORDERS
Diabetes & Endocrine System --- GLUCOSE METABOLISM DISORDERS
Diabetes --- DIABETES MELLITUS
Diabetes & Endocrine System --- DIABETES MELLITUS
Diabetes --- ENDOCRINE SYSTEM DISEASES
Diabetes & Endocrine System --- ENDOCRINE SYSTEM DISEASES
MeSH Terms
LACTOSE INTOLERANCE
GLUCOSE INTOLERANCE
DIABETES MELLITUS, TYPE 2
MALABSORPTION SYNDROMES
INTESTINAL DISEASES
GASTROINTESTINAL DISEASES
DIGESTIVE SYSTEM DISEASES
CARBOHYDRATE METABOLISM, INBORN ERRORS
METABOLISM, INBORN ERRORS
GENETIC DISEASES, INBORN
CONGENITAL, HEREDITARY, AND NEONATAL DISEASES AND ABNORMALITIES
METABOLIC DISEASES
NUTRITIONAL AND METABOLIC DISEASES
HYPERGLYCEMIA
GLUCOSE METABOLISM DISORDERS
DIABETES MELLITUS
ENDOCRINE SYSTEM DISEASES