A Clinical Trial of Metformin to Decrease Glucocorticoids Side Effects in Patients With Autoimmune Uveitis

Uveitis Clinical Trial

Official title:

Multicenter, Randomized, Controlled Clinical Trial Research Evaluating the Use of Combination Therapy of Glucocorticoids and Metformin to Decrease Glucocorticoids Side Effects in Patients With Autoimmune Uveitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03525028
• Other study ID #: 2017KY-06
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2018
• Est. completion date: January 1, 2023

Study information

• Verified date: May 2022
• Source: Tianjin Medical University
• Contact: Xiaomin Zhang, M.D.
• Phone: +86-13920023990
• Email: xiaomzh[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This project is designed to evaluating the use of combination therapy of glucocorticoid and metformin to decrease glucocorticoid side effects in participants with autoimmune uveitis.This study also aims to evaluate the anti-inflammatory and immunosuppressive effects of combination therapy.

Description:

Approval of the study was obtained from the hospital's ethical committee. The study design and methodology followed the tenets of Declaration of Helsinki. All participants were provided with written informed consent and received a thorough explanation of the study design, aims, and the side effect of metformin. This is a multicenter, randomized, controlled clinical trial research. According to 1:1 ratio, all participants are randomly divided into two groups, the metformin group and placebo group. According to the fasting blood glucose (FBG), triglycerides (TG),total cholesterol (TC) and body mass index (BMI), the investigators compared experimental group with control group to evaluate whether the use of combination therapy of glucocorticoid and metformin decrease glucocorticoid side effects in participants with autoimmune uveitis. According to best corrected visual acuity (BCVA), anterior chamber and vitreous inflammation, fluorescence fundus angiography (FFA), electroretinogram (ERG) and so on, the investigators evaluate the anti-inflammatory and immunosuppressive effects of metformin in treatment of autoimmune uveitis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 138
• Est. completion date: January 1, 2023
• Est. primary completion date: January 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Attending Tianjin Medical University Eye Hospital, ophthalmology department of Peking Union Medical College Hospital, ophthalmology department of Peking University First Hospital and Zhongshan Ophthalmic Center Sun Yat-sen University from January 2018 to January 2022.

2. Chronic and non-infectious autoimmune uveitis with systemic glucocorticoids treatment (Initiation dosage = 1 mg/kg/d or = 50 mg/d).

3. FBG < 6.1 mmol/L, HbAlc<6.O%, TC <6.2 mmol/L(240 mg/d1) and TG <2.3 mmol/L(200 mg/dl).

4. All genders, age = 18 years old.

5. Ready for systemic glucocorticoids treatment.

6. Willing to follow all study requirements and sign the informed consent.

7. Without history of cancer and serious systemic diseases.

Exclusion Criteria:

1. Participate in other clinical trials within the preceding one years

2. Planning ophthalmologic surgery over the next three months.

3. With other sight-threatening diseases except cataract, such as glaucoma, diabetic retinopathy, retinal detachment, and so on.

4. Taking or will take immunosuppressants which affecting glycometabolism and lipid metabolism except methotrexate,mycophenolate and azathioprine.

5. Any known history of a serious infection (e.g., HIV, hepatitis, pneumonia, syphilis or tuberculosis).

6. Any known history of diabetes mellitus, severe hepatic, renal or heart disease.

7. Any known history of drug addiction, drug abuse and malignant tumor.

8. Presence of a transplanted solid organ.

9. Pregnant women and nursing mothers.

10. Any known history of mental disorders.

Related Conditions & MeSH terms

• Glucocorticoid
• Metformin
• Uveitis

Intervention

Drug:
• Metformin
The investigators assumed that the combination therapy of metformin and glucocorticoids can decrease glucocorticoids side effects and synergia the anti-inflammatory and immune inhibitory effect of glucocorticoids. So the investigators use metformin in the experimental group.
• Placebo
The investigators use placebo in the control group.

Locations

Country	Name	City	State
China	Tianjin Medical University Eye Hospital	Tianjin	Tianjin

Sponsors (4)

Lead Sponsor	Collaborator
Tianjin Medical University	Peking Union Medical College Hospital, Peking University First Hospital, Zhongshan Ophthalmic Center, Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (10)

Del Barco S, Vazquez-Martin A, Cufí S, Oliveras-Ferraros C, Bosch-Barrera J, Joven J, Martin-Castillo B, Menendez JA. Metformin: multi-faceted protection against cancer. Oncotarget. 2011 Dec;2(12):896-917. Review. — View Citation

den Uyl D, van Raalte DH, Nurmohamed MT, Lems WF, Bijlsma JW, Hoes JN, Dijkmans BA, Diamant M. Metabolic effects of high-dose prednisolone treatment in early rheumatoid arthritis: balance between diabetogenic effects and inflammation reduction. Arthritis — View Citation

Gulliford MC, Charlton J, Latinovic R. Risk of diabetes associated with prescribed glucocorticoids in a large population. Diabetes Care. 2006 Dec;29(12):2728-9. — View Citation

Hoes JN, van der Goes MC, van Raalte DH, van der Zijl NJ, den Uyl D, Lems WF, Lafeber FP, Jacobs JW, Welsing PM, Diamant M, Bijlsma JW. Glucose tolerance, insulin sensitivity and ß-cell function in patients with rheumatoid arthritis treated with or withou — View Citation

Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016 Jul 15;48(7):e245. doi: 10.1038/emm.2016.81. Review. — View Citation

Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005 Jan;1(1):15-25. Review. — View Citation

Oray M, Abu Samra K, Ebrahimiadib N, Meese H, Foster CS. Long-term side effects of glucocorticoids. Expert Opin Drug Saf. 2016;15(4):457-65. doi: 10.1517/14740338.2016.1140743. Epub 2016 Feb 6. Review. — View Citation

Pasieka AM, Rafacho A. Impact of Glucocorticoid Excess on Glucose Tolerance: Clinical and Preclinical Evidence. Metabolites. 2016 Aug 3;6(3). pii: E24. doi: 10.3390/metabo6030024. Review. — View Citation

Perez A, Jansen-Chaparro S, Saigi I, Bernal-Lopez MR, Miñambres I, Gomez-Huelgas R. Glucocorticoid-induced hyperglycemia. J Diabetes. 2014 Jan;6(1):9-20. doi: 10.1111/1753-0407.12090. Epub 2013 Oct 29. Review. — View Citation

Schäcke H, Döcke WD, Asadullah K. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. 2002 Oct;96(1):23-43. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of abnormal metabolic indexes	The assessments of abnormal metabolic indexes include any of these outcome measures: FBG=6.1 mmol/L, TC=6.2 mmol/L (240 mg/d1), TG=2.3 mmol/L (200 mg/dl) or BMI increased 1 kg/m^2 than before in the process of follow-up twice in a row.	24 weeks