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

NCT07065942 | Recruiting

• 1 other identifier: I-23PJ993
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus; Constipation - Functional

Keywords

Diabetes; Constipation; Lactulose; Gut Microbiota; Metabolism

Outcome Measures

Primary Outcomes (3)

• Changes in Constipation Symptom Scores Pre- and Post-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)

  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

  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 Outcomes (2)

• Changes in Fasting Blood Glucose and Glycated Albumin Levels

  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)

  From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment

Study Arms (2)

Lactulose Oral Solution

ACTIVE COMPARATOR

Drug: Lactulose oral solution

Lactulose Oral Solution+Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules

EXPERIMENTAL

Drug: Lactulose oral solution; Drug: Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules

Interventions

Lactulose oral solution DRUG

Oral, 30 mL once daily administered during breakfast.

Lactulose Oral Solution; Lactulose Oral Solution+Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules

Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules DRUG

Oral, 2 tablets (500 mg per tablet) three times daily (TID).

Lactulose Oral Solution+Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-70 years
• Type 2 Diabetes Diagnosis (per 2017 ADA criteria), meeting ≥1 of:
• Fasting plasma glucose (FPG) ≥7.0 mmol/L
• hour plasma glucose ≥11.1 mmol/L during 75g anhydrous oral glucose tolerance test (OGTT)
• Random plasma glucose ≥11.1 mmol/L with hyperglycemia symptoms or hyperglycemic crisis
• Functional Constipation (Rome IV criteria), requiring:
• ≥2 of the following
• occurring in ≥25% of defecations
• Straining
• Lumpy/hard stools (Bristol Stool Scale 1-2)
• Sensation of incomplete evacuation
• Anorectal obstruction/blockage
• Manual maneuvers required
• \<3 spontaneous bowel movements/week
• No loose stools without laxatives

You may not qualify if:

• 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:
• Cardiopulmonary insufficiency
• Cerebrovascular diseases
• Psychiatric disorders
• Recent use (within 1 month) of confounding medications:
• Probiotics/prebiotics
• Antibiotics
• Laxatives (e.g., osmotic/stimulant agents)
• Prokinetics

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Beijing Hospital: collaborator
• Beijing Huaxin Hospital: collaborator
• Beijing Luhe Hospital: collaborator
• Beijing Huairou Hospital: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus; Constipation

Interventions

Lactulose

Condition Hierarchy (Ancestors)

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)

Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• Jingnan Li, MD, Ph.D

  Peking Union Medical College Hospital

  STUDY CHAIR

Central Study Contacts

Yaowen Hu

CONTACT

+86 18811618952; 1440556437@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician, Professor

Study Record Dates

• First Submitted: July 4, 2025
• First Posted: July 15, 2025
• Study Start: July 1, 2023
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: July 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)