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| ID | Type | Description | Link |
|---|---|---|---|
| lzp-2023/1-0422 | Other Grant/Funding Number | Latvian Council of Science |
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Study population: Type 2 diabetes patients Design of the study: Randomized, two-arm, placebo-controlled, and prospective crossover cohort study.
Objective: To evaluate the effects of interactions between metformin and traditionally used polyherbal formulations on gut microbiota in a prospective crossover study involving type 2 diabetes mellitus patients.
Sample size: 66 patients. Duration of study: 06/2024 - 12/2026
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Polyherbal formulation | Experimental | Participants in this arm will receive an add-on polyherbal formulation (PHF). Treatment Duration: 24 weeks, followed by a crossover to the placebo arm. |
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| Placebo | Placebo Comparator | Participants in this arm will receive a placebo. Treatment Duration: 24 weeks, followed by a crossover to the PHF arm. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Polyherbal Formulation (PHF) | Dietary Supplement | Description: A polyherbal formulation with known beneficial effects on gut microbiota and metabolic regulation. The formulation contains selected plant extracts studied for their hypoglycemic, antioxidant, and gut microbiota-modulating properties. Administration: Oral, daily dosage as per study protocol. Supplier: Arya Vaidya Pharmacy (AVP), Coimbatore, India (GMP-certified). |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Glycemic Control (HbA1c Levels) | Measurement of HbA1c (%) to evaluate the impact of PHF on glycemic control compared to placebo. | Baseline, Week 24, Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Relative Abundance of Key Bacterial Taxa in Gut Microbiota | Description: Measurement of the relative abundance of specific bacterial taxa (Akkermansia muciniphila, Escherichia spp., Intestinibacter) in fecal samples using metagenomic sequencing. | Baseline, Week 2, Week 24, Week 25, Week 48 |
| Gastrointestinal Tolerability of Metformin |
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Inclusion Criteria:
Participants must meet all of the following criteria to be eligible for enrollment:
Clinical diagnosis of Type 2 Diabetes Mellitus (T2D) HbA1c level between 6.5% and 8.5% On a stable dose of oral antidiabetic therapy for at least 6 months Age: ≥ 25 years and ≤ 80 years History of metformin intolerance, defined as previously reported gastrointestinal side effects or inability to tolerate full-dose metformin Willing and able to provide written informed consent Willing to comply with study procedures, including stool sample collection and continuous glucose monitoring (CGM)
Exclusion Criteria:
Participants will be excluded if they meet any of the following criteria:
Type 1 Diabetes Mellitus Current or recent (last 6 months) use of polyherbal formulations (PHF) Pregnancy or breastfeeding
Severe diabetic complications, such as:
Diabetic ketoacidosis Proliferative retinopathy Chronic kidney disease Stage IIIb or higher (eGFR <45 mL/min/1.73m²)
Recent cardiovascular events (within the last 6 months), including:
Stroke Myocardial infarction Unstable angina Heart failure
Severe systemic disease that could interfere with participation, such as:
Active cancer Severe autoimmune disease Current antibiotic therapy (within 2 months of study enrollment) Use of probiotics or prebiotics (within 1 month of study enrollment)
Severe gastrointestinal conditions, including:
Inflammatory bowel disease Chronic diarrhea of unknown origin Severe infection requiring antibacterial therapy Participation in another interventional study within the last 3 months
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pauls Stradins Clinical University Hospital | Riga | LV-1002 | Latvia |
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| Placebo | Other | Type: Placebo Comparator Description: A placebo formulation that matches PHF in appearance, texture, and administration schedule. Administration: Oral, daily dosage as per study protocol. |
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| Metformin (Standard Treatment for Type 2 Diabetes) | Drug | Description: Metformin is an FDA and EMA-approved antihyperglycemic medication that improves glycemic control by reducing hepatic glucose production and enhancing insulin sensitivity. Administration: Oral, per standard dosing guidelines. Availability: Provided to all participants per the national reimbursement scheme for T2D patients in Latvia. |
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Assessment of gastrointestinal side effects, including nausea, bloating, diarrhea, and abdominal discomfort, using a standardized gut microbiota-related symptom questionnaire. Scale Name: Gastrointestinal Symptom Rating Scale (GSRS) Score Range: Minimum = 0, Maximum = 4 Interpretation: Lower scores indicate better gastrointestinal tolerability. |
| Baseline, Week 2, Week 24, Week 25, Week 48 |
| Fasting and Postprandial Blood Glucose Levels | Measurement of fasting and postprandial glucose levels using standard biochemical assays. Unit of Measure: mmol/L | Baseline, Week 24, Week 48 |
| Time in Range (TIR) Measured by Continuous Glucose Monitoring (CGM) | Time in Range (TIR) Measured by Continuous Glucose Monitoring (CGM) Description: Measurement of the percentage of time that blood glucose levels remain within the target range (70-180 mg/dL) using data from Continuous Glucose Monitoring (CGM). | Week 1 |
| Metabolomic Analysis of Stool Samples (Short-chain fatty acids (SCFAs)) | The levels of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, valeric acid, and caproic acid will be quantified using gas chromatography-mass spectrometry (GC-MS). These concentrations will be reported in micromoles per gram of fecal matter (μmol/g). | Baseline, Week 24, Week 48 |
| Patient-Reported Outcomes on Quality of Life | Description: Evaluation using a validated diabetes-related quality of life questionnaire. Diabetes Quality of Life (DQOL) Questionnaire. Scoring: Items are scored on a 5-point Likert scale, with higher scores typically indicating more negative impacts or dissatisfaction. | Baseline, Week 24, Week 48 |
| Metabolomic Analysis of Stool Samples (Amino acids) | The following amino acids will be analyzed using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS): acetylcarnitine, arginine, butyrylcarnitine, carnitine, citrulline, creatinine, glutamic acid, glutamine, histidine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serotonin, taurine, tryptophan, tyrosine, and valine. Results will be expressed in nanomoles per gram of fecal matter (nmol/g). | Baseline, Week 24, Week 48 |
| Metabolomic Analysis of Stool Samples (Bile acids) | The bile acids to be measured include cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid, along with their conjugated forms: glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, taurocholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, taurolithocholic acid, and ursodeoxycholic acid. These will be quantified using liquid chromatography-mass spectrometry (LC-MS), with concentrations reported in micromoles per gram of fecal matter (μmol/g). | Baseline, Week 24, Week 48 |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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