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

Fresenius Kabi

Status and phase: Completed; Phase 4

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Glucose; Drug: Lactulose liquid 30 g; Drug: Lactulose crystals 30 g; Drug: Lactulose crystals 20 g; Drug: Still water; Drug: Lactulose liquid 20 g

Study type: Interventional

Funder types: Industry

Identifiers

NCT03666546

Lact-004-CP4

2018-002359-14 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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24 participants in 6 patient groups, including a placebo group

Laevolac crystals 20 g

Experimental group

Description:

Lactulose crystals, oral intake, 20 g single dose

Treatment:

Drug: Lactulose crystals 20 g

Laevolac crystals 30 g

Experimental group

Description:

Lactulose crystals, oral intake, 30 g single dose

Treatment:

Drug: Lactulose crystals 30 g

Laevolac liquid 20 g

Experimental group

Description:

Lactulose liquid, oral intake, 20 g single dose

Treatment:

Drug: Lactulose liquid 20 g

Laevolac liquid 30 g

Experimental group

Description:

Lactulose liquid, oral intake, 30 g single dose

Treatment:

Drug: Lactulose liquid 30 g

Glucose 30 g

Active Comparator group

Description:

Glucose Monohydrate, oral intake, 33 g single dose

Treatment:

Drug: Glucose

Water

Placebo Comparator group

Description:

Still water, oral intake, 250 mL single dose

Treatment:

Drug: Still water