Clinical trial NCT06442150: LCMD for Type 2 Diabetes Remission: Evaluation of Effectiveness and Exploration of Individual Differences
Official title: Low-Calorie Medicinal Diet for Type 2 Diabetes Remission: Evaluation of Effectiveness and Exploration of Individual Differences
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Type 2 Diabetes Mellitus in Obese
Type 2 Diabetes
Keywords: Remission of type 2 diabetes
Low Calorie Diet
Medicined Diet
Brain-Gut-Microbiome axis
Lead sponsor: Shanghai Municipal Hospital of Traditional Chinese Medicine
Sponsor class: OTHER
First posted: 2024-06-04
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: Type 2 diabetes (T2DM) has become a major public health problem. Achieving remission (HbA1c\<6.5% without glucose-lowering medications) has recently become a new treatment goal. Low-calorie diets effectively induce remission, but adverse effects like fatigue, appetite, and constipation hinder success. Integrating traditional Chinese medicine (TCM) herbs into a low-calorie diet may alleviate adverse effects and improve remission rates.

This project investigates the efficacy of a Low-Calorie Medicine Diet (LCMD) in achieving T2DM remission among overweight/obese individuals through a randomized controlled trial. The investigators will explore individual differences in remission and elucidate the underlying biological mechanisms, focusing on the brain-gut-microbiota axis. By integrating nutrition and TCM dietetics, this project provides a novel, evidence-based approach to managing T2DM in Chinese populations.

Detailed description: Type 2 diabetes (T2DM) has become a major public health problem, and effective prevention and treatment strategies are urgently needed. Recently, the understanding of T2DM has shifted to "a disease that can be remission." Achieving remission, defined as HbA1c\<6.5% without using glucose-lowering medications, has become a new treatment goal for T2DM. Evidence suggests that a low-calorie diet is an effective approach to induce remission. Our previous research (NCT05472272) also demonstrated that a low-calorie diet can achieve remission in Chinese T2DM patients.

However, adverse effects during the intervention, such as fatigue, appetite, and constipation, have become significant barriers to successful remission. These symptoms often result in poor adherence to the intervention plan and, consequently, failure to achieve remission. In traditional Chinese medicine (TCM), fatigue and constipation are typical symptoms of "Qi Vacuity", while hunger is more associated with "Yin Vacuity". "Herb is the food" is a unique concept in TCM. Integrating TCM herbs into a low-calorie diet may help alleviate these adverse effects and improve the likelihood of achieving diabetes remission.

This project aims to investigate the efficacy of a Low-Calorie Medicine Diet (LCMD) in achieving remission of T2DM among overweight/obese individuals through a randomized controlled trial. The investigators will also explore individual differences in achieving remission and elucidate the underlying biological mechanisms, focusing on the brain-gut-microbiota axis. By integrating theories from nutrition and TCM dietetics, this project seeks to provide a novel, evidence-based approach to the management of T2DM in Chinese populations.

Eligibility criteria: Inclusion Criteria:

* Physician-diagnosed T2DM
* The history of T2DM less than 6 years
* Most recent HbA1c higher than 6.5%
* Body mass index: 24-45 kg/m2
* Fasting C-p ≥1.1 ng/ml
* Inability to provide informed consent

Exclusion Criteria:

* Type 1 diabetes, type 2 diabetes currently treated with insulin, or HbA1c ≥12%
* Cardiovascular events within 6 months before trial
* Current use of anti-obesity medications, eating disorders, dieting behaviors, or weight loss \>5 kg within 6 months before trial
* Chronic kidney disease stage 3b or above (eGFR \<30 mL/min/1.73m²)
* Any condition causing fluid overload, such as heart failure or liver cirrhosis
* Previously diagnosed psychiatric disorders (e.g., schizophrenia, post-traumatic stress disorder, obsessive-compulsive disorder), uncontrolled depression, or epilepsy
* Severe arthritis or active gout
* Active gallstone disease or known as asymptomatic gallstones
* Concurrent enrollment in another clinical trial
* Pregnancy, lactation, or planned conception during the study
* Substance abuse
* Known malignancy
* Comorbidities increasing dietary intervention risk (e.g., biliary disorders)
* Long-term use of antibiotics, corticosteroids, NSAIDs, or PPIs
* Chronic gastrointestinal disorders affecting gut microbiota (e.g., ulcerative colitis)
* Severe hepatic impairment (ALT \>2.5× ULN)
* Inability to provide informed consent

Primary outcomes:
measure: Number of participants achieving diabetes remission as assessed by American Diabetes Association criteria
timeFrame: Baseline to 24 and 52 weeks
measure: Number of participants achieving significant weight loss, defined as a reduction of at least 12kg from baseline body weight
timeFrame: Baseline to 12, 24 and 52 weeks
Secondary outcomes:
measure: Change from baseline in insulin sensitivity as assessed by insulin tolerance test
timeFrame: Baseline to 12, 24 and 52 weeks
measure: Change from baseline in beta cell function as assessed by arginine stimulation test
timeFrame: Baseline to 12, 24 and 52 weeks
measure: Change from baseline in liver fat content and pancreatic fat content as assessed by magnetic resonance imaging
timeFrame: Baseline to 12, 24 and 52 weeks
measure: Change from baseline in plasma glucose concentration
timeFrame: Baseline to 12, 24 and 52 weeks
measure: Change from baseline in fasting serum lipid levels, including total cholesterol, LDL-C, HDL-C, and triglycerides
timeFrame: Baseline to 12, 24 and 52 weeks
measure: Change from baseline in brain functional connectivity and activity as assessed by functional magnetic resonance imaging
timeFrame: Baseline to 12, 24 and 52 weeks
measure: Change from baseline in gut microbiota composition and its metabolites as assessed by 16S rRNA gene sequencing and metabolomics analysis
timeFrame: Baseline to 12, 24 and 52 weeks
measure: Change from baseline in the quality of life score as assessed by a validated questionnaire (e.g., SF-36, EQ-5D)
timeFrame: Baseline to 12, 24 and 52 weeks
measure: Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
timeFrame: 12, 24 and 52 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Municipal Hospital of Traditional Chinese Medicine
state: Shanghai
Study officials:
affiliation: Shanghai Municipal Hospital of Traditional Chinese Medicine
name: Feng Tao, M.D.
role: PRINCIPAL_INVESTIGATOR
References: