Clinical trial NCT04698330: Effects Of Berberine Plus Inulin On Diabetes Care in Patients With LADA
Official title: Effects of Berberine Plus Inulin on Diabetes Care in Patients With Latent Autoimmune Diabetes in Adults: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Type 1 Diabetes Mellitus
Autoimmune Diabetes
Keywords: LADA
Berberine
Inulin
Diabetes Care
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
First posted: 2021-01-06
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to evaluate the effects of oral berberine (BBR) and inulin combined with insulin therapy on diabetes care in patients with LADA.

Detailed description: Latent autoimmune diabetes in adults (LADA) is a hybrid form of diabetes, characterized by autoimmune destruction of pancreatic β-cells as well as insulin resistance and is triggered by environmental factors in the context of genetic susceptibility. Meanwhile，blood glucose management is the cornerstone of diabetes care and poor glycemic control will cause a series of diabetes complications. This study will focus on improving the quality of life of LADA patients and blood glucose management as the starting point to explore the improvement effects of combined drugs on the development of diabetes.

Inulin is a common prebiotic that has been shown to improve glycemic control, alter the gut microbiota and suppress inflammation. Berberine(BBR), a small alkaloid isolated from medicinal plants, has been reported to have many therapeutic effects, including anti-bacteria, anti-diabetes, and lipid-lowering. Besides, studies revealed that BBR exerts antidiabetic effects by modulating gut microbiota. In a multicentre, randomized, double-blinded, placebo-controlled 12-week clinical trial conducted in 409 drug-naive T2D patients, Wang et al. confirmed the hypoglycaemic effect of BBR in Chinese participants and demonstrated the BBR-induced changes in the human gut microbiome in comparison with the placebo. Moreover, Ho et al. conducted a randomized, placebo-controlled trial in 38 children with type 1 diabetes using placebo or prebiotic oligofructose-enriched inulin for 12 weeks, and found that oral supplement of the prebiotic could improve glycemic status and β cell function. So we speculate that BBR and inulin combination can also improve glycemic control in the patients with LADA.

This study is a prospective, randomized, double-blind, placebo-controlled trial. The study comprises once screening, the 1-month run-in period, the 3-month treatment period and the 9-month follow-up period. After obtaining the informed consent from the patient who is willing to participate the 3-month treatment will enter to the 1-month run-in period. According to the inclusion/exclusion criteria, the eligible patients will be randomized to the 3-month treatment period. Patients will be randomized into four groups : BBR-alone, inulin+BBR, inulin-alone, or placebo. The primary outcome is to assess the change in glycated hemoglobin levels. Dynamic blood glucose parameters, β-cell function and gut microbiota, as well as adverse events and quality of life will be monitored.

Eligibility criteria: Inclusion Criteria:

1. Diabetes diagnosed according to the report of WHO in 1999；
2. Meet the Chinese Diabetes Society diagnostic criteria (2012) for LADA: (1)glutamic acid decarboxylase antibody (GADA) positive; (2) age at diagnosis ≧ 18 years old; (3) independent on insulin for more than 6 months after diagnosis;
3. Aged between 18 and 70 years old;
4. 7.0%≤HbA1c ≤10.0%;
5. BMI ≥ 18.5 kg/m2, and no more than 37.5 kg/m2;
6. Written informed consent from the patient or family representative.

Exclusion Criteria:

1. Severe liver dysfunction (ALT and AST greater than 3 times the upper limit of detection);
2. eGFR \< 50ml/(min • 1.73 m2);
3. Evidence of acute or chronic infection affecting glycemic control within 4 weeks prior to the first visit;
4. History of any malignancy;
5. Pregnancy, breastfeeding, or planned pregnancy during the study period;
6. Secondary diabetes;
7. Presence of acute complications (ketoacidosis, lactic acidosis or hyperosmolar coma);
8. Severe organic heart disease, including but not limited to congenital heart disease, rheumatic heart disease, hypertrophic or dilated cardiomyopathy, etc., New York Heart Association (NYHA) heart function classification ≥Grade III;
9. Chronic use of systemic glucocorticoids or other immunosuppressive agents for over 3 months，or use of antibiotic medications or other interventions that could affect the gastrointestinal tract for 2 months before the screening and during the whole study period.
10. History of hemolytic anemia or glucose-6-phosphate dehydrogenase deficiency.
11. Allergic to berberine or any components in the combinations.

Primary outcomes:
measure: Change in HbA1c
timeFrame: 1 year after start of trial
Secondary outcomes:
measure: Change in C-peptide
timeFrame: 1 year after start of trial
measure: Incidence of acute and chronic diabetes complications
timeFrame: 1 year after start of trial
measure: Change in gut permeability
timeFrame: 1 year after start of trial
measure: Change in gut microbiota composition
timeFrame: 1 year after start of trial
measure: Assessment of quality of life
timeFrame: 1 year after start of trial
measure: Gastrointestinal side effects and other drug-related side effects
timeFrame: 1 year after start of trial
measure: Hypoglycemic events
timeFrame: 1 year after start of trial
Other outcomes:
Locations:
city: Changsha
country: China
facility: Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University
state: Hunan
Study officials:
affiliation: Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, China
name: Yang Xiao, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang Y, Gu Y, Ren H, Wang S, Zhong H, Zhao X, Ma J, Gu X, Xue Y, Huang S, Yang J, Chen L, Chen G, Qu S, Liang J, Qin L, Huang Q, Peng Y, Li Q, Wang X, Kong P, Hou G, Gao M, Shi Z, Li X, Qiu Y, Zou Y, Yang H, Wang J, Xu G, Lai S, Li J, Ning G, Wang W. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nat Commun. 2020 Oct 6;11(1):5015. doi: 10.1038/s41467-020-18414-8.
citation: Ho J, Nicolucci AC, Virtanen H, Schick A, Meddings J, Reimer RA, Huang C. Effect of Prebiotic on Microbiota, Intestinal Permeability, and Glycemic Control in Children With Type 1 Diabetes. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4427-4440. doi: 10.1210/jc.2019-00481.
citation: Zhang R, Xiao Y, Yan J, Yang W, Wu X, Mei Z, Zhou Z. Effects of Berberine Plus Inulin on Diabetes Care in Patients With Latent Autoimmune Diabetes in Adults: Protocol for a Randomized Controlled Trial. Front Endocrinol (Lausanne). 2022 Jun 15;13:876657. doi: 10.3389/fendo.2022.876657. eCollection 2022.