Condition category
Nutritional, Metabolic, Endocrine
Date applied
19/07/2015
Date assigned
09/09/2015
Last edited
08/09/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Gut microbiota is the term used to refer to the bacteria that naturally live in our intestines. It has an effect on numerous biological functions. Recent research suggests that its composition (i.e. what type of bacteria is making up the microbiota) may contribute to the development of metabolic disorders, such as diabetes, by affecting the physiology and metabolism of an individual. Metformin is one of the most widely prescribed type 2 diabetes (T2DM) treatments. Metformin-induced changes in the gut microbiota have been reported; however, the relationship between metformin treatment and the gut microbiota remains unclear. This study investigates whether the anti-diabetic effect of metformin is related to changes in the composition of gut microbiota.

Who can participate?
Adults aged between 18-79 with T2DM, treated with two or more oral anti-diabetic drugs for at least 3 months and a BMI≥18.5kg/m2

What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 are given insulin plus metformin. Those in group 2 are given insulin only. The study takes place over a 16 week period during which time changes in gut microbiota are measured once a month.

What are the possible benefits and risks of participating?
The metformin treatment may be related to alterations of intestinal microbial composition and improve a participants T2DM directly or indirectly. There is a risk that the treatment may be of no benefit.

Where is the study run from?
Qilu Hospital ,Shandong University (China)

When is the study starting and how long is it expected to run for?
June 2015 to January 2016

Who is funding the study?
Qilu Hospital, Shandong University (China)

Who is the main contact?
Mr Anju Zuo

Trial website

Contact information

Type

Scientific

Primary contact

Mr Anju Zuo

ORCID ID

Contact details

107 Wenhua W Rd
Lixia
Jinan
Shandong
250012
China

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

2015041

Study information

Scientific title

A prospective, randomized, open-label, parallel controlled, single-center trial, examining the effect of Metformin on gut microbiota and pancreatic beta cells function in patients with type 2 diabetes

Acronym

Study hypothesis

1. The gut microbiota and their metabolic pathways will be influenced by Metformin treatment in patients with type 2 diabetes
2. Metformin maybe ameliorate islet function by improving dysbiosis of gut micobiota in patients with type 2 diabetes

Ethics approval

Ethical Committee of drug clinical trials, Qilu Hospital, Shandong University, 25/05/2015, ref: 2015041

Study design

Prospective, randomized, open-label, parallel controlled, single-center trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Type 2 diabetes (T2DM) patients with oral anti-diabetic drugs (OAD) losing efficacy

Intervention

1. 30 patients with OAD losing efficacy receiving insulin plus metformin
2. 30 patients with OAD losing efficacy receiving insulin monotherapy

Intervention was for 16 weeks.

Intervention type

Phase

Drug names

Primary outcome measures

Identifying the change of composition of gut microbiota by 16s rRNA technology

Measured once a month over the study period.

Secondary outcome measures

1. Achievement of HbA1c
2. Achievement of weight loss
3. Change in HbA1c
4. Waist circumference
5. Fasting blood glucose
6. Lipids and CRP
7. LPS,IL-6mRNA,IL-1BmRNA,CD4/CD8 and Foxp3Tre

They will be measured once a month.

Overall trial start date

25/07/2015

Overall trial end date

25/01/2016

Reason abandoned

Eligibility

Participant inclusion criteria

1. Diagnosed with T2DM
2. Treated with two or more OADs for more than three months with blood glucose HbA1c≥7% within 14 days of the screening day
3. Aged between 18 to 79
4. BMI≥18.5kg/m2
5. According to investigators’ judgment, subjects are able and willing to obey the following instructions:
5.1. During the whole study, treatment will be continued according to the requirements in the protocol
5.2. During the whole study, diet will be maintained according to the requirements in the protocol
5.3. Participation in regular visits, and willing to receive telephone follow-up
5.4. Women that are able to conceive (and men whose partner can conceive) are willing to be given contraceptive treatment during the whole study
6. Participants must be male, or non-pregnant females who are not breastfeeding
7. Participants must be without metformin contraindications
8. All participants must sign informed consent form before any study relevant activities have been conducted

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

1. Participants diagnosed with type 1 diabetes
2. Previously treated with insulin for more than 14 days continuously within 3 months before screening visit or within one month before the patient entering the study
3. Diagnosed with any of the following cardiovascular diseases within three months before screening visit: acute myocardial infarction, heart function classification III/IV according to New York Heart
Association, congestive heart failure with left ventricular ejection fraction ≤ 40%, or cerebrovascular events (apoplexy)
4. Impaired liver function, with obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or ALT/AST levels ≥2.0 times of the upper limit of the reference range at the screening visit
5. Serum creatinine ≥1.5mg/dl (133 μmol/L) for men, ≥1.4mg/dl (124 μmol/L) for womenor eGFR<45ml/min/1.73m2
6. Known to have proliferative retinopathy or maculopathy which needs an urgent treatment by the investigator’s judgment
7. Repeated severe hypoglycemia and hypoglycemia consciousness disorders by investigators’ judgment
8. Persistent uncontrolled hypertension (systolic blood pressure ≥180mmHg, or diastolic blood pressure ≥105mmHg)
9. Severe chronic gastrointestinal diseases
10. History of diabetic ketoacidosis or hypertonia condition/coma once or more than once;
11. Receiving long-term (>14 days) systemic glucocorticoid treatment (external use, intraocular, inhaled or intranasal preparations except) or received this type of treatment within four weeks before screening visit; During the whole study, any treatment which can affect glucose regulation should be avoided, as thyroid medication, estrogen, oral contraceptives, phenytoin, niacin, sympathomimetic drugs and isoniazid
12. Hematological system diseases which maybe affect HbA1c value (as hemolytic anemia, sickle cell disease)
13. Any conditions which may affect patients follow and complete the study protocol (as known drug abuse, alcoholic, mental diseases)
14. Currently in a study or 30 days before recruiting withdrawing from a study which involves the investigational medicinal product or not approved drugs or instruments; or participating other types of clinical studies at the same time and not suitable to participate in this study judged by investigators from medical or science perspectives
15. Allergic to metformin/insulin or with metformin/insulin contraindication
16. Combined with severe lung diseases or history of hypoxia
17. Combined with endocrine diseases as hypercortisolism; patients with thyroid diseases under control of drugs for more than half year can be included;
18. Stress state as surgery, acute craniocerebral injury etc
19. Vitamin B12 deficiency without correction

Recruitment start date

25/07/2015

Recruitment end date

30/01/2016

Locations

Countries of recruitment

China

Trial participating centre

Qilu Hospital, Shandong University
107 Wenhua W Rd Lixia Jinan
Shandong
250012
China

Sponsor information

Organisation

Qilu Hospital, Shandong University

Sponsor details

107 Wenhua W Rd
Lixia
Jinan
Shandong
250012
China

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

Qilu Hospital, Shandong University

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

We plan to present our study results in a year and intend to publish it in relevant magazines such as Diabetic Research.

Intention to publish date

01/10/2016

Participant level data

Other

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes