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

NCT03666546 | Completed Phase 4

• 2 other identifiers: Lact-004-CP42018-002359-14
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Blood glucose; Diabetes Mellitus, Type 2; Lactulose; Constipation; Oral intake

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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

Other Outcomes (4)

• Adverse Events (AEs)

  up to 64 days

• Gastrointestinal tolerability: global scaled evaluation

  180 minutes and 24 hours post-dose

• Gastrointestinal tolerability: diarrhoea, distension, rumbling, nausea, vomiting, burping, regurgitation/heartburn, flatulence, abdominal discomfort, abdominal pain

  180 minutes and 24 hours post-dose

Study Arms (6)

Laevolac crystals 20 g

EXPERIMENTAL

Lactulose crystals, oral intake, 20 g single dose

Drug: Lactulose crystals 20 g

Laevolac crystals 30 g

EXPERIMENTAL

Lactulose crystals, oral intake, 30 g single dose

Drug: Lactulose crystals 30 g

Laevolac liquid 20 g

EXPERIMENTAL

Lactulose liquid, oral intake, 20 g single dose

Drug: Lactulose liquid 20 g

Laevolac liquid 30 g

EXPERIMENTAL

Lactulose liquid, oral intake, 30 g single dose

Drug: Lactulose liquid 30 g

Glucose 30 g

ACTIVE COMPARATOR

Glucose Monohydrate, oral intake, 33 g single dose

Drug: Glucose

Water

PLACEBO COMPARATOR

Still water, oral intake, 250 mL single dose

Drug: Still water

Interventions

Lactulose crystals 20 g DRUG

White or almost white crystalline powder. The product will be provided in sachets to be dissolved in 250 mL water.

Also known as: Laevolac crystals 20 g

Laevolac crystals 20 g

Lactulose crystals 30 g DRUG

White or almost white crystalline powder. The products will be provided in sachets to be dissolved in 250 mL water.

Also known as: Laevolac crystals 30 g

Laevolac crystals 30 g

Lactulose liquid 20 g DRUG

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.

Also known as: Laevolac liquid 20 g

Laevolac liquid 20 g

Lactulose liquid 30 g DRUG

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.

Also known as: Laevolac liquid 30 g

Laevolac liquid 30 g

Glucose DRUG

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.

Also known as: Glucose Monohydrate

Glucose 30 g

Still water DRUG

250 mL still water will be used. Water from the same source will be also used to dissolve investigational and control products

Also known as: Water

Water

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fresenius Kabi: lead

Study Sites (1)

Clinical Research Center (CRC)

Graz, A-8036, Austria

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Constipation

Interventions

Glucose; Water

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Thomas Pieber, Prof. MD

  Head and Chair of Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University, Graz, Austria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: September 12, 2018
• Study Start: November 26, 2018
• Primary Completion: March 5, 2019
• Study Completion: March 8, 2019
• Last Updated: April 12, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)