Clinical trial NCT03666546: Blood Glucose Response After Oral Intake of Lactulose in Mildly Constipated Patients With Diabetes Mellitus Type 2
Official title: Blood Glucose Response After Oral Intake of Lactulose (Laevolac®) in Mildly Constipated Patients With Diabetes Mellitus Type 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Keywords: Blood glucose
Diabetes Mellitus, Type 2
Lactulose
Constipation
Oral intake
Lead sponsor: Fresenius Kabi
Sponsor class: INDUSTRY
First posted: 2018-09-12
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Patients with non-insulin requiring diabetes mellitus type 2 treated with diet and oral antidiabetics and/or Glucagon-like Peptide 1 receptor agonists
2. Age: 18-75 years
3. Female and male
4. Caucasian
5. HbA1c ≤ 7.5 %
6. Stable treatment, i.e. no change in diabetes mellitus related medication within the last 3 months
7. 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
8. Availability and presence in the trial unit for approx. 4 hours/ week for 4 weeks
9. 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
10. Signed informed consent form

Exclusion Criteria:

1. Fasting blood glucose \<4.4 mmol/L (\<80 mg/dL) or \>10 mmol/L (\>180 mg/dL) (capillary)
2. BMI \<18.5 kg/m² or ≥35 kg/m²
3. Change in body weight ≥10 % within the last 3 months
4. Smoker
5. Major medical or surgical event requiring hospitalization within the last 3 months
6. Acute gastrointestinal diseases including diarrhea and/or vomiting within the last 2 weeks
7. 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)
8. Not willing to abstain from laxatives 2 days before the visits 1-4 and up to 24h after visits 1-4
9. 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
10. Severe liver, renal or cardiac disease
11. Hereditary problems of galactose or fructose intolerance, lactase deficiency or glucose-galactose malabsorption
12. 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
13. Known or suspected allergy to the investigational drug(s) or other components of the study drug(s)
14. 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
15. Known history of human immunodeficiency virus (HIV), hepatitis B and/or C
16. Pregnancy, lactation
17. Clinically relevant findings as established by medical history, physical examination, clinical laboratory and/or vital signs
18. 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

Primary outcomes:
measure: 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)]
timeFrame: 0 - 180 minutes, during 4 study visits
Secondary outcomes:
measure: Maximum blood glucose concentration (Cmax)
timeFrame: 0 - 180 minutes, during 4 study visits
measure: Maximum increase of blood glucose concentration (Max_increase)
timeFrame: 0 - 180 minutes, during 4 study visits
measure: Relative maximum increase of blood glucose concentration (Max_increase_rel)
timeFrame: 0 - 180 minutes, during 4 study visits
measure: Time to reach maximum blood glucose concentration (Tmax)
timeFrame: 0 - 180 minutes, during 4 study visits
measure: Total area under curve from 0 to 180 minutes for blood glucose concentration (AUC(0-180 minutes))
timeFrame: 0 - 180 minutes, during 4 study visits
measure: 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))
timeFrame: 0 - 180 minutes, during 4 study visits
Other outcomes:
measure: Adverse Events (AEs)
timeFrame: up to 64 days
measure: Gastrointestinal tolerability: global scaled evaluation
timeFrame: 180 minutes and 24 hours post-dose
measure: Gastrointestinal tolerability: diarrhoea, distension, rumbling, nausea, vomiting, burping, regurgitation/heartburn, flatulence, abdominal discomfort, abdominal pain
timeFrame: 180 minutes and 24 hours post-dose
measure: Blood glucose concentration at 240 minutes - only when blood glucose is >10 mmol/L (>180 mg/dL) at 180 minutes
timeFrame: 240 minutes post-dose
Locations:
city: Graz
country: Austria
facility: Clinical Research Center (CRC)
Study officials:
affiliation: Head and Chair of Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University, Graz, Austria
name: Thomas Pieber, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: