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
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 measure
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 (if study stopped)
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
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
Basic results (scientific)
Publication list