Blood Glucose Response After Oral Intake of Lactulose in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
Prospective, open, mono-center, randomized, two part study with 4-way cross-over design in each study part. The objective of the study is to investigate blood glucose levels after oral intake of defined amounts of lactulose.

Official Title
-----------------
Blood Glucose Response After Oral Intake of Lactulose in Healthy Volunteers

Conditions
-----------------
Blood Glucose

Intervention / Treatment
-----------------
* Dietary Supplement: Lactulose crystals 10 g
* Dietary Supplement: Lactulose crystals 20 g
* Dietary Supplement: Lactulose liquid 10 g
* Dietary Supplement: Lactulose liquid 20 g
* Dietary Supplement: Oral glucose 20 g
* Dietary Supplement: Still water


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy volunteers Age: 18-65 years Approx. 3-5 bowel movements per week Caucasian Availability and presence in the trial unit for approx. 4 hours/ week for 4 times in a row with approx. 1 week of washout in between Signed informed consent form Exclusion Criteria: Known (family) history of diabetes mellitus or use of anti-hyperglycaemic drugs or Insulin Clinically relevant renal or hepatic disease, liver enzymes > 10% above reference range Fasting blood glucose > 100 mg/dL or HbA1c outside of reference range Total cholesterol > 250 mg/dL or triglycerides > 150 mg/dL Haemoglobin < 11 g/dL (women); < 12.5 g/dL (men) BMI < 19 kg/m² and ≥ 30 kg/m² Intentional and unintentional weight loss > 5% in the previous 6 months Smoker Major medical or surgical event requiring hospitalization within the previous 3 months Presence of disease or drug(s) influencing digestion and absorption of nutrients or bowel habits Intake of medications known to affect glucose tolerance, e.g., steroids, protease inhibitors or antipsychotics (stable doses of e.g., oral contraceptives, thyroxin, vitamins and mineral supplements or drugs to treat hypertension or osteoporosis are acceptable) Chronic intake of substances affecting blood coagulation (e.g. acetylic acid, anticoagulants, diuretics, thiazides), which in the investigator's opinion would impact volunteer safety Hereditary problems of galactose or fructose intolerance, lactase deficiency or glucose-galactose malabsorption Suspicion of drug abuse Abuse of alcoholic drinks, defined as an average daily intake of more than one litre of beer per day or equivalent amount of alcohol in other beverages Pregnant or breast feeding women Known or suspected allergy to any component of the investigational product(s) Known HIV-infection Known acute or chronic hepatitis B and C infection Blood donation within 4 weeks prior to visit 1 or during the study Volunteer unable to co-operate adequately Participation in a clinical trial with an investigational product within one month before start of study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study arm 1<br>Lactulose crystals 10 g vs lactulose crystals 20 g vs oral glucose 20 g vs still water | Dietary Supplement: Lactulose crystals 10 g<br>* White or almost white crystalline powder used as food ingredient. The products will be provided in sachets to be dissolved in 250 mL water.<br>Dietary Supplement: Lactulose crystals 20 g<br>* White or almost white crystalline powder used as food ingredient. The products will be provided in sachets to be dissolved in 250 mL water.<br>Dietary Supplement: Oral glucose 20 g<br>* White crystalline powder used as food ingredient. To standardise for 20 g glucose, 22 g glucose monohydrate will be used. The products will be provided in sachets to be dissolved in 250 mL water.<br>* Other names: glucose monohydrate;Dietary Supplement: Still water<br>* Still water will be used. Water from the same source will be also used to dissolve investigational and control products.<br>|
| Active Comparator: Study arm 2<br>Lactulose liquid 10 g vs lactulose liquid 20 g vs oral glucose 20 g vs still water | Dietary Supplement: Lactulose liquid 10 g<br>* Clear, viscous liquid, colourless or pale brownish-yellow liquid syrup (solution). The products will be provided in sachets to be dissolved in 250 mL water.<br>Dietary Supplement: Lactulose liquid 20 g<br>* Clear, viscous liquid, colourless or pale brownish-yellow liquid syrup (solution). The products will be provided in sachets to be dissolved in 250 mL water.<br>Dietary Supplement: Oral glucose 20 g<br>* White crystalline powder used as food ingredient. To standardise for 20 g glucose, 22 g glucose monohydrate will be used. The products will be provided in sachets to be dissolved in 250 mL water.<br>* Other names: glucose monohydrate;Dietary Supplement: Still water<br>* Still water will be used. Water from the same source will be also used to dissolve investigational and control products.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Capillary blood glucose levels as incremental area under the curve (iAUC) above baseline (iAUC(0-180min)) |  | 0-180 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum blood glucose concentration (Cmax) |  | 0-180 min | 
| Maximum increase of blood glucose concentration (Max_increase) | Cmax minus baseline value | 0-180 min | 
| Relative maximum increase of blood glucose concentration(Max_increase rel) | Cmax / baseline value | 0-180 min | 
| Time to reach maximum blood glucose concentration (Tmax) |  | 0-180 min | 
| First time to reach baseline again after increase or decrease in blood glucose (Tbaseline) |  | 0-180 min | 
| Total area under curve from 0 to 180 min for blood glucose concentration (AUC(0-180min)) |  | 0-180 min | 
| Baseline corrected area under curve from 0 to 180 min for blood glucose concentration (AUCbase_c(0-180min)) | Area under curve from 0 to 180 min minus baseline*180min | 0-180 min | 
| Adverse events (AEs) |  | After screening till study day 22 (+24 hours) | 
| Gastrointestinal tolerability (assessed by subject's questionnaire) |  | 180 min | 
| Gastrointestinal tolerability (assessed by subject's questionnaire) |  | 24 hours post-dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Blood glucose level, Oral intake, Lactulose, Healthy volunteers