Effects of Lactulose on Gut Microbiota and Metabolism in Diabetic Constipated Patients

July 4, 2025 updated by: Jing-Nan Li, Peking Union Medical College Hospital

Constipation is the most common gastrointestinal manifestation in diabetic patients. Emerging evidence suggests that gut microbiota dysbiosis may contribute to the pathogenesis of diabetes, highlighting the need to investigate its role in diabetic constipation, though current research remains limited.

Current management of diabetic constipation primarily relies on bulk-forming and osmotic laxatives. Additionally, microbiome-modulating agents (e.g., probiotics, prebiotics, and synbiotics) may serve as adjunctive therapies by regulating gut microbiota and enhancing intestinal motility. Lactulose, a well-tolerated osmotic laxative with prebiotic effects, is widely recommended in clinical guidelines. It promotes short-chain fatty acid production, increases fecal volume, and accelerates colonic transit, thereby alleviating constipation. However, its specific impact on gut microbiota composition and metabolic pathways in diabetic constipation remains unclear.

This study aims to explore changes in fecal microbiota and metabolomic profiles in diabetic patients with chronic constipation following treatment with lactulose alone or in combination with Bacillus subtilis-Enterococcus faecium probiotics, providing mechanistic insights into prebiotic therapy for this condition.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China
        • Recruiting
        • Peking Union Medical College Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age: 18-70 years

  • Type 2 Diabetes Diagnosis (per 2017 ADA criteria), meeting ≥1 of:

    1. Fasting plasma glucose (FPG) ≥7.0 mmol/L
    2. hour plasma glucose ≥11.1 mmol/L during 75g anhydrous oral glucose tolerance test (OGTT)
    3. Random plasma glucose ≥11.1 mmol/L with hyperglycemia symptoms or hyperglycemic crisis

  • Functional Constipation (Rome IV criteria), requiring:

    1. ≥2 of the following

      1. occurring in ≥25% of defecations
      2. Straining
      3. Lumpy/hard stools (Bristol Stool Scale 1-2)
      4. Sensation of incomplete evacuation
      5. Anorectal obstruction/blockage
      6. Manual maneuvers required
      7. <3 spontaneous bowel movements/week
    2. No loose stools without laxatives
    3. Exclusion of IBS diagnosis. Symptom duration >6 months, with active symptoms meeting criteria for last 3 months.
  • Stable Glycemic Control: No anticipated antidiabetic medication adjustments during study
  • Dietary Stability: Maintain consistent diet; avoid yogurt, fermented foods, prebiotic-containing processed foods, or other items that may confound results

Exclusion Criteria:

  • Secondary Constipation due to organic diseases or medication effects.
  • Constipation-predominant Irritable Bowel Syndrome (IBS-C).
  • Concurrent gastrointestinal disorders (e.g., inflammatory bowel disease, colorectal cancer).
  • Type 1 Diabetes Mellitus.

  • Severe chronic comorbidities, including:

    1. Cardiopulmonary insufficiency
    2. Cerebrovascular diseases
    3. Psychiatric disorders

  • Recent use (within 1 month) of confounding medications:

    1. Probiotics/prebiotics
    2. Antibiotics
    3. Laxatives (e.g., osmotic/stimulant agents)
    4. Prokinetics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lactulose Oral Solution
Drug: Lactulose oral solution
Oral, 30 mL once daily administered during breakfast.
Experimental: Lactulose Oral Solution+Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules
Drug: Lactulose oral solution
Oral, 30 mL once daily administered during breakfast.
Drug: Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules
Oral, 2 tablets (500 mg per tablet) three times daily (TID).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Constipation Symptom Scores Pre- and Post-Treatment
Time Frame: From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment
Assessment of treatment efficacy on constipation symptoms: Changes in symptom scores from baseline to post-treatment within each treatment arm and comparative analysis between the lactulose monotherapy group and lactulose+Medilac-S combination therapy group
From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment
Changes in Fecal Microbiota Composition (16S rRNA and Metagenomics)
Time Frame: From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment
Comparison of Fecal Microbiota Composition Changes (16S rRNA and Metagenomics): Pre- vs. Post-Treatment Alterations and Intergroup Differences Between Lactulose Monotherapy and Lactulose+Medilac-S Combination Therapy
From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment
Temporal Changes in Fecal Untargeted Metabolomics Profiles
Time Frame: From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment
Temporal Changes in Fecal Untargeted Metabolomics Profiles: Pre- vs. post-treatment alterations and comparative analysis between lactulose monotherapy and lactulose+Medilac-S combination groups.
From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Fasting Blood Glucose and Glycated Albumin Levels
Time Frame: From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment
Changes in Fasting Blood Glucose and Glycated Albumin Levels: Pre- vs. post-treatment variations and comparative analysis between lactulose monotherapy and lactulose+Medilac-S combination groups
From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment
Changes in Blood Lipid Profiles (Total Cholesterol, Triglycerides, HDL-C, and LDL-C)
Time Frame: From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment
Changes in Blood Lipid Profiles (Total Cholesterol, Triglycerides, HDL-C, and LDL-C): Pre- vs. post-treatment alterations and comparative analysis between lactulose monotherapy and lactulose+Medilac-S combination therapy groups
From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Collaborators

Beijing Hospital
Beijing Luhe Hospital
Beijing Huairou Hospital
Beijing Huaxin Hospital

Investigators

  • Study Chair: Jingnan Li, MD, Ph.D, Peking Union Medical College Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2023

Primary Completion (Estimated)

July 30, 2026

Study Completion (Estimated)

July 30, 2026

Study Registration Dates

First Submitted

July 4, 2025

First Submitted That Met QC Criteria

July 4, 2025

First Posted (Actual)

July 15, 2025

Study Record Updates

Last Update Posted (Actual)

July 15, 2025

Last Update Submitted That Met QC Criteria

July 4, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I-23PJ993

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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