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Prevention of Metabolic Complications of Glucocorticoid Excess

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ClinicalTrials.gov Identifier: NCT01319994
Recruitment Status : Unknown
Verified July 2012 by Marta Korbonits, Barts & The London NHS Trust.
Recruitment status was:  Recruiting
First Posted : March 22, 2011
Last Update Posted : July 26, 2012
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Glucocorticoid Treatment Drug: Metformin Drug: Placebo Phase 2 Phase 3

Detailed Description:

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Prevention of Metabolic Complications of Glucocorticoid Excess - a Randomised, Doubleblind,Placebo Controlled Study
Study Start Date : September 2010
Estimated Primary Completion Date : January 2015
Estimated Study Completion Date : January 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Metformin
Metformin treatment
Drug: Metformin
Metformin treatment
Placebo Comparator: Placebo
Placebo treatment
Drug: Placebo
Placebo treament


Outcome Measures

Primary Outcome Measures :
  1. CT abdomen [ Time Frame: 3 months ]
    change in liver fat


Secondary Outcome Measures :
  1. HOMA [ Time Frame: 3 months ]
    This is a measurement of insulin sensitivity


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients diagnosed with a rheumatological disease and not started yet on GC treatment or • Rheumatology patients treated with GC >20mg/d 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

Exclusion Criteria:

  • prior therapy with metformin during the last 6 months
  • 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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01319994


Contacts
Contact: Marta Korbonits m.korbonits@qmul.ac.uk
Contact: Sam Owusu-Antwi s.Owusu-Antwi@qmul.ac.uk

Locations
United Kingdom
Barts and the London Recruiting
London, United Kingdom
Sponsors and Collaborators
Barts & The London NHS Trust
Barts and the London School of Medicine and Dentistry
Investigators
Principal Investigator: Marta Korbonits, MD, PhD Barts and The London
More Information

Responsible Party: Marta Korbonits, Professor, Barts & The London NHS Trust
ClinicalTrials.gov Identifier: NCT01319994     History of Changes
Other Study ID Numbers: 09/H1102/82
First Posted: March 22, 2011    Key Record Dates
Last Update Posted: July 26, 2012
Last Verified: July 2012

Keywords provided by Marta Korbonits, Barts & The London NHS Trust:
glucocorticoid

Additional relevant MeSH terms:
Metformin
Glucocorticoids
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists