Effects Of Berberine Plus Inulin On Diabetes Care in Patients With LADA

NCT ID: NCT04698330

Last Updated: 2022-02-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-31
• Study Completion Date: 2026-12-31

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.

Conditions

Type 1 Diabetes Mellitus; Autoimmune Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Group A

LADA patients are assigned to receive berberine and inulin for 3-month.

Group Type: EXPERIMENTAL

Berberine

Intervention Type: DRUG

0.6g (6 pills) of Berberine tablets administered twice a day orally before meal for 3 months

Inulin

Intervention Type: DRUG

0.6g (6 pills) of Inulin tablets administered twice a day orally before meal for 3 months

Group B

LADA patients are assigned to receive berberine and placebo(for inulin) for 3-month.

Group Type: EXPERIMENTAL

Berberine

Intervention Type: DRUG

0.6g (6 pills) of Berberine tablets administered twice a day orally before meal for 3 months

Inulin placebo tablets

Intervention Type: DRUG

0.6g (6 pills) of Inulin placebo tablets administered twice a day orally before meal for 3 months

Group C

LADA patients are assigned to receive placebo(for berberine) and inulin for 3-month.

Group Type: EXPERIMENTAL

Inulin

Intervention Type: DRUG

0.6g (6 pills) of Inulin tablets administered twice a day orally before meal for 3 months

Berberine placebo tablets

Intervention Type: DRUG

0.6g (6 pills) of Berberine placebo tablets administered twice a day orally before meal for 3 months

Group D

LADA patients are assigned to receive placebo(for berberine) and placebo(for inulin) for 3-month.

Group Type: PLACEBO_COMPARATOR

Berberine placebo tablets

Intervention Type: DRUG

0.6g (6 pills) of Berberine placebo tablets administered twice a day orally before meal for 3 months

Inulin placebo tablets

Intervention Type: DRUG

0.6g (6 pills) of Inulin placebo tablets administered twice a day orally before meal for 3 months

Interventions

Berberine

0.6g (6 pills) of Berberine tablets administered twice a day orally before meal for 3 months

Intervention Type: DRUG

Inulin

0.6g (6 pills) of Inulin tablets administered twice a day orally before meal for 3 months

Intervention Type: DRUG

Berberine placebo tablets

0.6g (6 pills) of Berberine placebo tablets administered twice a day orally before meal for 3 months

Intervention Type: DRUG

Inulin placebo tablets

0.6g (6 pills) of Inulin placebo tablets administered twice a day orally before meal for 3 months

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Xiangya Hospital of Central South University

OTHER

Sponsor Role: lead

Responsible Party

Yang Xiao

Associate Professor, Department of Metabolism and Endocrinology, Institute of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Second Xiangya Hospital, Central South University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yang Xiao, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, China

Locations

Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University

Changsha, Hunan, China

Countries

China

Central Contacts

Yang Xiao, MD/PhD

Role: CONTACT

xiaoyang29@csu.edu.cn

86-731-85292154

Facility Contacts

Yang Xiao, MD/PhD

Role: primary

xiaoyang29@csu.edu.cn

86-0731-85292154

References

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.

Reference Type: BACKGROUND

PMID: 33024120 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31188437 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35784546 (View on PubMed)

Other Identifiers

2020LADACP

Identifier Type: -

Identifier Source: org_study_id