Type 1 Diabetes MellitusPhase 4NCT04698330
Effects Of Berberine Plus Inulin On Diabetes Care in Patients With LADA
A Phase 4 study testing Berberine and Inulin in people with Type 1 Diabetes Mellitus and Autoimmune Diabetes, run by Second Xiangya Hospital of Central South University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Type 1 Diabetes Mellitus, Autoimmune Diabetes
- What is being tested?
- Berberine and Inulin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 240 participants
- Where
- 1 siteChina
- Study dates
- May 2022to Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diabetes diagnosed according to the report of WHO in 1999；
- 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;
- Aged between 18 and 70 years old;
- 7.0%≤HbA1c ≤10.0%;
- BMI ≥ 18.5 kg/m2, and no more than 37.5 kg/m2;
- Written informed consent from the patient or family representative.
Who cannot join
- Severe liver dysfunction (ALT and AST greater than 3 times the upper limit of detection);
- eGFR < 50ml/(min • 1.73 m2);
- Evidence of acute or chronic infection affecting glycemic control within 4 weeks prior to the first visit;
- History of any malignancy;
- Pregnancy, breastfeeding, or planned pregnancy during the study period;
- Secondary diabetes;
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- Presence of acute complications (ketoacidosis, lactic acidosis or hyperosmolar coma);
- 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;
- 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.
- History of hemolytic anemia or glucose-6-phosphate dehydrogenase deficiency.
- Allergic to berberine or any components in the combinations.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University
Changsha, Hunan, 410011
Yang Xiao, MD/PhD, 86-0731-85292154, xiaoyang29@csu.edu.cn
About this study
Official title: Effects of Berberine Plus Inulin on Diabetes Care in Patients With Latent Autoimmune Diabetes in Adults: A Randomized Controlled Trial
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.
Read the 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
- Being tested
- Berberine, Inulin, Berberine placebo tablets, Inulin placebo tablets
- Keywords
- LADA, Berberine, Inulin, Diabetes Care
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BerberineDrug
0.6g (6 pills) of Berberine tablets administered twice a day orally before meal for 3 months
InulinDrug
0.6g (6 pills) of Inulin tablets administered twice a day orally before meal for 3 months
Berberine placebo tabletsDrug
0.6g (6 pills) of Berberine placebo tablets administered twice a day orally before meal for 3 months
Inulin placebo tabletsDrug
0.6g (6 pills) of Inulin placebo tablets administered twice a day orally before meal for 3 months
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | LADA patients are assigned to receive berberine and inulin for 3-month. Receives: Drug: Berberine; Drug: Inulin |
| Group B | Experimental | LADA patients are assigned to receive berberine and placebo(for inulin) for 3-month. Receives: Drug: Berberine; Drug: Inulin placebo tablets |
| Group C | Experimental | LADA patients are assigned to receive placebo(for berberine) and inulin for 3-month. Receives: Drug: Inulin; Drug: Berberine placebo tablets |
| Group D | Placebo comparator | LADA patients are assigned to receive placebo(for berberine) and placebo(for inulin) for 3-month. Receives: Drug: Berberine placebo tablets; Drug: Inulin placebo tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in HbA1c
The primary outcome measure is the change in mean HbA1c level, reflecting the blood glucose management status of the patients.
Measured: 1 year after start of trial
Secondary outcomes (7)
Change in C-peptide
C-peptide are measured before and after a mixed meal tolerance test.
Measured: 1 year after start of trial
Incidence of acute and chronic diabetes complications
In this study, the chronic diabetes complications recorded mainly include diabetic macrovascular disease, diabetic nephropathy, diabetic retinopathy and peripheral neuropathy.
Measured: 1 year after start of trial
Change in gut permeability
Gut permeability is measured by amount of mannitol and lactulose in urine.
Measured: 1 year after start of trial
Change in gut microbiota composition
The changes of gut microbiota are mainly detected by multi omics technology.
Measured: 1 year after start of trial
Assessment of quality of life
Quality of life will be assessed by the Chinese version of the Audit of Diabetes Dependent Quality of Life (ADDQoL-19).
Measured: 1 year after start of trial
Gastrointestinal side effects and other drug-related side effects
The gastrointestinal side effects need to be self-reported by the patient, such as nausea, vomiting, diarrhea, constipation, flatulence, etc.
Measured: 1 year after start of trial
Hypoglycemic events
Hypoglycemia events are divided into mild hypoglycemia and severe hypoglycemia.
Measured: 1 year after start of trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study startMay 2022 (estimated)
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Second Xiangya Hospital of Central South UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yang Xiao, Second Xiangya Hospital of Central South University
- Investigators
- Yang Xiao, MD/PhD, Principal investigator, Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04698330
- Sponsor's protocol ID
- 2020LADACP
- Status last verified
- Feb 2022
- First submitted
- 2 Jan 2021
- Last updated
- 25 Feb 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33024120Ho 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.
PubMed 31188437Zhang 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.
PubMed 35784546
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Berberine Plus Inulin on Diabetes Care in Patients With Latent Autoimmune Diabetes in Adults: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04698330
- Acronym / sponsor ID
- 2020LADACP
- Conditions
- Type 1 Diabetes Mellitus, Autoimmune Diabetes
- Keywords
- LADA, Berberine, Inulin, Diabetes Care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Second Xiangya Hospital of Central South UniversityUniversity, hospital or other
- Study start
- May 2022 (estimated)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 6 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Berberine, Drug: InulinLADA patients are assigned to receive berberine and inulin for 3-month. |
| Group B | Experimental | Drug: Berberine, Drug: Inulin placebo tabletsLADA patients are assigned to receive berberine and placebo(for inulin) for 3-month. |
| Group C | Experimental | Drug: Inulin, Drug: Berberine placebo tabletsLADA patients are assigned to receive placebo(for berberine) and inulin for 3-month. |
| Group D | Placebo comparator | Drug: Berberine placebo tablets, Drug: Inulin placebo tabletsLADA patients are assigned to receive placebo(for berberine) and placebo(for inulin) for 3-month. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diabetes diagnosed according to the report of WHO in 1999；
- 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;
- Aged between 18 and 70 years old;
- 7.0%≤HbA1c ≤10.0%;
- BMI ≥ 18.5 kg/m2, and no more than 37.5 kg/m2;
Key exclusion criteria (11 listed)
- Severe liver dysfunction (ALT and AST greater than 3 times the upper limit of detection);
- eGFR < 50ml/(min • 1.73 m2);
- Evidence of acute or chronic infection affecting glycemic control within 4 weeks prior to the first visit;
- History of any malignancy;
- Pregnancy, breastfeeding, or planned pregnancy during the study period;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Berberine0.6g (6 pills) of Berberine tablets administered twice a day orally before meal for 3 months | Drug | Group A, Group B |
| Inulin0.6g (6 pills) of Inulin tablets administered twice a day orally before meal for 3 months | Drug | Group A, Group C |
| Berberine placebo tablets0.6g (6 pills) of Berberine placebo tablets administered twice a day orally before meal for 3 months | Drug | Group C, Group D |
| Inulin placebo tablets0.6g (6 pills) of Inulin placebo tablets administered twice a day orally before meal for 3 months | Drug | Group B, Group D |
Primary outcome
Change in HbA1c
Time frame: 1 year after start of trial
The primary outcome measure is the change in mean HbA1c level, reflecting the blood glucose management status of the patients.
7 secondary outcomes
Change in C-peptide
Time frame: 1 year after start of trial
Incidence of acute and chronic diabetes complications
Time frame: 1 year after start of trial
Change in gut permeability
Time frame: 1 year after start of trial
Change in gut microbiota composition
Time frame: 1 year after start of trial
Assessment of quality of life
Time frame: 1 year after start of trial
Gastrointestinal side effects and other drug-related side effects
Time frame: 1 year after start of trial
Hypoglycemic events
Time frame: 1 year after start of trial
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2022.
- Background: PubMed 33024120Zhang 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.
- Background: PubMed 31188437Ho 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.
- Derived from this study: PubMed 35784546Zhang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yang Xiao, MD/PhD principal investigator
Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Berberine and Inulin in people with Type 1 Diabetes Mellitus and Autoimmune Diabetes, run by Second Xiangya Hospital of Central South University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 25 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yang Xiao, MD/PhD (86-731-85292154, xiaoyang29@csu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in HbA1c (time frame: 1 year after start of trial). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04698330, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2022.