Blood Glucose Response After Oral Intake of Lactulose in Mildly Constipated Patients With Diabetes Mellitus Type 2

Study Overview
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Brief Summary
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The objective of the study is to investigate whether lactulose, given orally as powder or liquid, increases blood glucose levels in patients with diabetes mellitus type 2. The dose of lactulose given in the study is normally used for treatment of constipation.

Official Title
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Blood Glucose Response After Oral Intake of Lactulose (Laevolac®) in Mildly Constipated Patients With Diabetes Mellitus Type 2

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Lactulose crystals 20 g
* Drug: Lactulose crystals 30 g
* Drug: Lactulose liquid 20 g
* Drug: Lactulose liquid 30 g
* Drug: Glucose
* Drug: Still water


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with non-insulin requiring diabetes mellitus type 2 treated with diet and oral antidiabetics and/or Glucagon-like Peptide 1 receptor agonists Age: 18-75 years Female and male Caucasian HbA1c ≤ 7.5 % Stable treatment, i.e. no change in diabetes mellitus related medication within the last 3 months Mild functional constipation according to modified Rome IV criteria fulfilled for the last 3 months with symptom onset at least 6 months before study start defined as: approx. 3-5 bowel movements per week, of which 1-2 usually cause discomfort e.g., straining, lumpy or hard stools, sensation of incomplete evacuation or anorectal obstructions/blockage Availability and presence in the trial unit for approx. 4 hours/ week for 4 weeks Women of childbearing potential must be using a medically approved method of contraception OR women must be postmenopausal for at least 12 months prior to study entry Signed informed consent form Exclusion Criteria: Fasting blood glucose <4.4 mmol/L (<80 mg/dL) or >10 mmol/L (>180 mg/dL) (capillary) BMI <18.5 kg/m² or ≥35 kg/m² Change in body weight ≥10 % within the last 3 months Smoker Major medical or surgical event requiring hospitalization within the last 3 months Acute gastrointestinal diseases including diarrhea and/or vomiting within the last 2 weeks Presence of disease or intake of drug(s) / supplements other than antidiabetic treatment influencing digestion and absorption of carbohydrates or bowel habits (intake of laxatives in general allowed with exception see next criterion) (dietary / supplementary fibres allowed if stable dose since 1 month before study start) Not willing to abstain from laxatives 2 days before the visits 1-4 and up to 24h after visits 1-4 Use of following medication/ supplementation within the last 4 weeks and during the study: Intake of medications other than antidiabetic treatment known to affect glucose tolerance e.g., steroids, protease inhibitors or antipsychotics; Intake of prebiotics or probiotics Chronic intake of substances affecting blood coagulation (e.g. acetylic acid (100 mg as standard prophylactic treatment allowed when dose is stable 1 month prior to screening), anticoagulants, diuretics, thiazides (diuretics and thiazides allowed e.g. for hypertension treatment when dose is stable 1 month prior to screening)), which in the investigator's opinion would impact patient safety Severe liver, renal or cardiac disease Hereditary problems of galactose or fructose intolerance, lactase deficiency or glucose-galactose malabsorption Suspicion of alcohol abuse (defined as an average daily intake of more than one litre of beer per day or equivalent amount of alcohol in other beverages) or drug abuse Known or suspected allergy to the investigational drug(s) or other components of the study drug(s) Acute inflammatory bowel disease (ulcerative colitis, Crohn's disease), gastrointestinal obstruction or subocclusive syndrome, perforations or risk of perforation in gastrointestinal tract, abdominal pain of undetermined cause Known history of human immunodeficiency virus (HIV), hepatitis B and/or C Pregnancy, lactation Clinically relevant findings as established by medical history, physical examination, clinical laboratory and/or vital signs Participation in another interventional study with an investigational drug or an investigational medical device within 30 days prior to start of study or during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laevolac crystals 20 g<br>Lactulose crystals, oral intake, 20 g single dose | Drug: Lactulose crystals 20 g<br>* White or almost white crystalline powder. The product will be provided in sachets to be dissolved in 250 mL water.<br>* Other names: Laevolac crystals 20 g;|
| Experimental: Laevolac crystals 30 g<br>Lactulose crystals, oral intake, 30 g single dose | Drug: Lactulose crystals 30 g<br>* White or almost white crystalline powder. The products will be provided in sachets to be dissolved in 250 mL water.<br>* Other names: Laevolac crystals 30 g;|
| Experimental: Laevolac liquid 20 g<br>Lactulose liquid, oral intake, 20 g single dose | Drug: 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>* Other names: Laevolac liquid 20 g;|
| Experimental: Laevolac liquid 30 g<br>Lactulose liquid, oral intake, 30 g single dose | Drug: Lactulose liquid 30 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>* Other names: Laevolac liquid 30 g;|
| Active Comparator: Glucose 30 g<br>Glucose Monohydrate, oral intake, 33 g single dose | Drug: Glucose<br>* White crystalline powder. To standardise for 30 g glucose, 33 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;|
| Placebo Comparator: Water<br>Still water, oral intake, 250 mL single dose | Drug: Still water<br>* 250 mL still water will be used. Water from the same source will be also used to dissolve investigational and control products<br>* Other names: Water;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Capillary blood glucose levels as baseline corrected AUC: AUCbaseline_c (0-180 minutes) [Baseline corrected area under curve from 0 to 180 minutes for blood glucose concentration (= Area under curve from 0 to 180 minutes minus baseline*180 minutes)] |  | 0 - 180 minutes, during 4 study visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum blood glucose concentration (Cmax) |  | 0 - 180 minutes, during 4 study visits | 
| Maximum increase of blood glucose concentration (Max_increase) |  | 0 - 180 minutes, during 4 study visits | 
| Relative maximum increase of blood glucose concentration (Max_increase_rel) |  | 0 - 180 minutes, during 4 study visits | 
| Time to reach maximum blood glucose concentration (Tmax) |  | 0 - 180 minutes, during 4 study visits | 
| Total area under curve from 0 to 180 minutes for blood glucose concentration (AUC(0-180 minutes)) |  | 0 - 180 minutes, during 4 study visits | 
| Incremental area under curve from 0 to 180 minutes for blood glucose concentration, i.e., above baseline levels for blood glucose concentration after oral intake of Laevolac crystals/liquid or control products (iAUC(0-180min)) |  | 0 - 180 minutes, during 4 study visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood glucose, Diabetes Mellitus, Type 2, Lactulose, Constipation, Oral intake