Prevention of Metabolic Complications of Glucocorticoid Excess

NCT01319994 | Completed Phase 2 Results DMC

• 1 other identifier: 09/H1102/82
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

According to current estimates, nearly 1% of the general population is treated with long-term glucocorticoids. Chronic hypercortisolism leads to a phenotype that resembles the metabolic syndrome. The investigators have shown that inhibition of adenosine-monophosphate-activated protein kinase (AMPK) activity in adipose tissue plays a role in corticosteroid-mediated insulin resistance. Metformin, one of the mainstay therapies for type 2 diabetes, is a known activator of AMPK, which mediates its beneficial effects on glucose and lipid metabolism. The investigators have shown in an animal model that metformin - via altering AMPK activity - prevents the development of the metabolic complications of glucocorticoid excess, and the investigators wish to confirm this in a human study. The aim of this prospective, randomised, double-blind, placebo-controlled study is to investigate the effect of metformin treatment on metabolic parameters in patients on long-term high-dose glucocorticoids. The study is part of the investigators translational project and could rapidly lead to immediate patient benefit, improving quality of life and reducing health care costs for the NHS.

Conditions

Iatrogenic Cushing Disease

Keywords

glucocorticoid

Outcome Measures

Primary Outcomes (1)

• CT Abdomen

  change in visceral/subcutaneous fat

  3 months minus baseline

Secondary Outcomes (1)

• HOMA2-IR

  3 months minus baseline

Study Arms (2)

Metformin

EXPERIMENTAL

Metformin 850mg TDS (12 weeks)

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Placebo 850mg TDS (12 weeks)

Drug: Placebo

Interventions

Metformin DRUG

Metformin 850mg TDS (12 weeks)

Also known as: metformin tablet containing 850mg metformin

Metformin

Placebo DRUG

Placebo 850mg TDS (12 weeks)

Also known as: Placebo tablet matching the active drug tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients diagnosed with an inflammatory condition and not started yet on GC treatment or • patients with an inflammatory condition treated with GC \>20mg/d of prednisolone (or its cumulative equivalent) for at least 4wks
• minimal duration of prospective therapy 12w
• dose of prednisolone ≥10mg/d (or equivalent GC)
• ambulatory patients
• patients \>18 years old
• ability to understand verbal and written instructions and informed consent

You may not qualify if:

• prior therapy with metformin during the last 6 months
• known pre-existing diabetes
• pregnancy
• breastfeeding
• liver impairment: ALT and/or AST ≥2.5 x UNL
• renal impairment: serum creatinine levels ≥135.0 µmol/L in males and ≥110.0 µmol/L in females
• current malignancy
• patients unable to give written informed consent
• or patients not understanding English

Sponsors & Collaborators

• Barts & The London NHS Trust: lead
• Barts and the London School of Medicine and Dentistry: collaborator

Study Sites (1)

Barts and the London

London, United Kingdom

Location

Related Publications (1)

• Pernicova I, Kelly S, Ajodha S, Sahdev A, Bestwick JP, Gabrovska P, Akanle O, Ajjan R, Kola B, Stadler M, Fraser W, Christ-Crain M, Grossman AB, Pitzalis C, Korbonits M. Metformin to reduce metabolic complications and inflammation in patients on systemic glucocorticoid therapy: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial. Lancet Diabetes Endocrinol. 2020 Apr;8(4):278-291. doi: 10.1016/S2213-8587(20)30021-8. Epub 2020 Feb 25.

  PMID: 32109422 DERIVED

MeSH Terms

Interventions

Metformin

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Prof M Korbonits
• Organization: Queen Mary University of London

m.korbonits@qmul.ac.uk

+442078826197

Study Officials

• Marta Korbonits, MD, PhD

  Barts and The London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 21, 2011
• First Posted: March 22, 2011
• Study Start: July 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: January 1, 2015
• Last Updated: April 12, 2019
• Results First Posted: April 12, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)