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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03666546
Recruitment Status : Completed
First Posted : September 12, 2018
Last Update Posted : April 12, 2019
Sponsor:
Information provided by (Responsible Party):
Fresenius Kabi

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 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 Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Blood Glucose Response After Oral Intake of Lactulose (Laevolac®) in Mildly Constipated Patients With Diabetes Mellitus Type 2
Actual Study Start Date : November 26, 2018
Actual Primary Completion Date : March 5, 2019
Actual Study Completion Date : March 8, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Laevolac crystals 20 g
Lactulose crystals, oral intake, 20 g single dose
Drug: Lactulose crystals 20 g
White or almost white crystalline powder. The product will be provided in sachets to be dissolved in 250 mL water.
Other Name: Laevolac crystals 20 g

Experimental: Laevolac crystals 30 g
Lactulose crystals, oral intake, 30 g single dose
Drug: Lactulose crystals 30 g
White or almost white crystalline powder. The products will be provided in sachets to be dissolved in 250 mL water.
Other Name: Laevolac crystals 30 g

Experimental: Laevolac liquid 20 g
Lactulose liquid, oral intake, 20 g single dose
Drug: Lactulose liquid 20 g
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.
Other Name: Laevolac liquid 20 g

Experimental: Laevolac liquid 30 g
Lactulose liquid, oral intake, 30 g single dose
Drug: Lactulose liquid 30 g
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.
Other Name: Laevolac liquid 30 g

Active Comparator: Glucose 30 g
Glucose Monohydrate, oral intake, 33 g single dose
Drug: Glucose
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.
Other Name: Glucose Monohydrate

Placebo Comparator: Water
Still water, oral intake, 250 mL single dose
Drug: Still water
250 mL still water will be used. Water from the same source will be also used to dissolve investigational and control products
Other Name: Water




Primary Outcome Measures :
  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)] [ Time Frame: 0 - 180 minutes, during 4 study visits ]

Secondary Outcome Measures :
  1. Maximum blood glucose concentration (Cmax) [ Time Frame: 0 - 180 minutes, during 4 study visits ]
  2. Maximum increase of blood glucose concentration (Max_increase) [ Time Frame: 0 - 180 minutes, during 4 study visits ]
  3. Relative maximum increase of blood glucose concentration (Max_increase_rel) [ Time Frame: 0 - 180 minutes, during 4 study visits ]
  4. Time to reach maximum blood glucose concentration (Tmax) [ Time Frame: 0 - 180 minutes, during 4 study visits ]
  5. Total area under curve from 0 to 180 minutes for blood glucose concentration (AUC(0-180 minutes)) [ Time Frame: 0 - 180 minutes, during 4 study visits ]
  6. 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)) [ Time Frame: 0 - 180 minutes, during 4 study visits ]

Other Outcome Measures:
  1. Adverse Events (AEs) [ Time Frame: up to 64 days ]
    Adverse Events will be documented from start of fasting on the day before Screening until the day after the last study Intervention. This is up to 64 days, depending on the day of Screening (21 to 3 days before the first study Intervention) and on the duration of wash out phases between interventions.

  2. Gastrointestinal tolerability: global scaled evaluation [ Time Frame: 180 minutes and 24 hours post-dose ]
    Gastrointestinal tolerability will be assessed by the patients by means of a global scaled evaluation with "Very good", "Good", "Moderate", or "Poor".

  3. Gastrointestinal tolerability: diarrhoea, distension, rumbling, nausea, vomiting, burping, regurgitation/heartburn, flatulence, abdominal discomfort, abdominal pain [ Time Frame: 180 minutes and 24 hours post-dose ]
    The single gastrointestinal symptoms will be assessed by the patients using a 4-point Likert scale: "No symptoms or discomfort", "Mild symptoms or discomfort", "Moderate symptoms of discomfort", or "Severe symptoms of discomfort".

  4. Blood glucose concentration at 240 minutes - only when blood glucose is >10 mmol/L (>180 mg/dL) at 180 minutes [ Time Frame: 240 minutes post-dose ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03666546


Locations
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Austria
Clinical Research Center (CRC)
Graz, Austria, A-8036
Sponsors and Collaborators
Fresenius Kabi
Investigators
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Principal Investigator: Thomas Pieber, Prof. MD Head and Chair of Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University, Graz, Austria

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Responsible Party: Fresenius Kabi
ClinicalTrials.gov Identifier: NCT03666546    
Other Study ID Numbers: Lact-004-CP4
2018-002359-14 ( EudraCT Number )
First Posted: September 12, 2018    Key Record Dates
Last Update Posted: April 12, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fresenius Kabi:
Blood glucose
Diabetes Mellitus, Type 2
Lactulose
Constipation
Oral intake
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Methamphetamine
Lactulose
Gastrointestinal Agents
Central Nervous System Stimulants
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Dopamine Uptake Inhibitors