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

Not Applicable

Recruiting

• Conditions: Diabetes Mellitus; Constipation - Functional
• Interventions: Drug: Lactulose oral solution; Drug: Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules

• Registration Number: NCT07065942
• Lead Sponsor: Peking Union Medical College Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-07-01
• Status Verified: 2025-06
• Study First Submitted: 2025-07-04
• Study First Submitted QC: 2025-07-04
• Last Update Submitted: 2025-07-04
• Study First Posted: 2025-07-15
• Last Update Posted: 2025-07-15
• Primary Completion: 2026-07-30
• Study Completion: 2026-07-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lactulose Oral Solution	Lactulose oral solution	-
Lactulose Oral Solution+Live Combined B. Subtilis and E. Faecium Enteric-coated Capsules	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	-

Primary Outcome Measures

Name	Time	Method
Changes in Constipation Symptom Scores Pre- and Post-Treatment	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
Changes in Fecal Microbiota Composition (16S rRNA and Metagenomics)	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
Temporal Changes in Fecal Untargeted Metabolomics Profiles	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.

Secondary Outcome Measures

Name	Time	Method
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 Fasting Blood Glucose and Glycated Albumin Levels: Pre- vs. post-treatment variations and comparative analysis between lactulose monotherapy and lactulose+Medilac-S combination groups
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	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

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China