Prevention of Metabolic Complications of Glucocorticoid Excess
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Prevention of Metabolic Complications of Glucocorticoid Excess - a Randomised, Doubleblind,Placebo Controlled Study|
- CT abdomen [ Time Frame: 3 months ] [ Designated as safety issue: No ]change in liver fat
- HOMA [ Time Frame: 3 months ] [ Designated as safety issue: No ]This is a measurement of insulin sensitivity
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
2 Study Aims and Objectives To investigate the effect of metformin treatment on metabolic parameters in patients with long-term high dose GCs.
3 Study Design 3.1 General Design We will recruit patients (18-75y) with excess glucocorticoids either because they have Cushing's syndrome or they have inflammatory conditions requiring GC treatment (e.g. rheumatoid arthritis, giant cell arteritis/polymyalgia rheumatica) into a pilot, randomised, double-blind, placebo-controlled trial. These patients will be treated with metformin to prevent or reverse their metabolic complications. Prevention algorithm: Patients who are about to start GC treatment predictably for ≥12w at a ≥10mg/d prednisolone (or equivalent) dose who consent to participate in this study will be randomly assigned to receive either placebo (20 patients/group, see power calculations) or metformin at the maximum tolerated dose with a minimum of 850 mg bd for 12w. Treatment algorithm: Consenting patients already on long-term GC treatment (≥4w, ≥20mg/d) who are expected to continue for at least 12w at ≥10mg/d prednisolone will be randomly assigned to receive either placebo or metformin for 12w. In both algorithms, metformin treatment will be started gradually (as standard practice) to avoid gastrointestinal side effects and the full dose will be reached by day 10. Patients will have a full clinical assessment before the start of the metformin treatment and at the end of the 12w treatment period. Anthropometric and biochemical parameters and questionnaires will be repeated at 4 and 8 weeks.
Patients with endogenous Cushing's syndrome will be randomly assigned to receive either placebo (10 patients/group) or metformin at the maximum tolerated dose with a minimum of 850 mg bd for 4 weeks. Patients will have a full clinical assessment before the start of the metformin treatment and at the end of the 4w treatment period.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01319994
|Contact: Marta Korbonitsfirstname.lastname@example.org|
|Contact: Sam Owusu-Antwi||s.Owusu-Antwi@qmul.ac.uk|
|Barts and the London||Recruiting|
|London, United Kingdom|
|Principal Investigator:||Marta Korbonits, MD, PhD||Barts and The London|