A Phase 2/3 interventional study of Metformin and Placebo in Iatrogenic Cushing Disease, sponsored by Barts & The London NHS Trust. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2019-04-12.
Sponsored by Barts & The London NHS Trust · Phase 2/3, Interventional, and Treatment
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.
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) requiring glucocorticoid treatment for various inflammatory conditions (e.g. rheumatoid arthritis, giant cell arteritis/polymyalgia rheumatic, asthma, sarcoidosis) 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 prednisolone or equivalent) 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.
64 studies on the registry are indexed under Pituitary ACTH Hypersecretion; 16 are open to participants now.
This study's enrollment of 57 is above the median of 44 across 40 interventional studies indexed under Pituitary ACTH Hypersecretion.
Browse Pituitary ACTH Hypersecretion studies →Barts & The London NHS Trust is the lead sponsor of 151 studies on the registry; 21 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metformin 850mg TDS (12 weeks)
Drug: Metformin
Placebo 850mg TDS (12 weeks)
Drug: Placebo
Metformin 850mg TDS (12 weeks)
Also known as: metformin tablet containing 850mg metformin
Placebo 850mg TDS (12 weeks)
Also known as: Placebo tablet matching the active drug tablet
CT Abdomen
change in visceral/subcutaneous fat
Time frame: 3 months minus baseline
HOMA2-IR
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-IR is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin resistance which is the reciprocal of insulin sensitivity (%S)(100/%S) as a percentage of a normal reference population (normal young adults). HOMA2-IR is calculated using the HOMA model: www.dtu.ox.ac.uk/homacalculator/
Time frame: 3 months minus baseline
| Milestone | Metformin | Placebo |
|---|---|---|
| Started | 26 | 27 |
| Abto keep appoinment shedule | 23 | 24 |
| Tolerated at least 1.7g/day dose | 19 | 24 |
| Glucocorticoid dose as inc cri | 19 | 22 |
| Did not develop overt diabetes | 19 | 21 |
| Completed | 19 | 21 |
| Not completed | 7 | 6 |
| Withdrew: Protocol violation | 7 | 6 |
change in visceral/subcutaneous fat
| ratio | Metformin | Placebo |
|---|---|---|
| CT Abdomen | 0.08 ± 0.19 | -0.03 ± 0.22 |
The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-IR is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin resistance which is the reciprocal of insulin sensitivity (%S)(100/%S) as a percentage of a normal reference population (normal young adults). HOMA2-IR is calculated using the HOMA model: www.dtu.ox.ac.uk/homacalculator/
| HOMA score | Metformin | Placebo |
|---|---|---|
| HOMA2-IR | 0.22 ± 3.26 | 2.35 ± 3.23 |
Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Metformin | — | 1/26 (3.8%) | 26/26 (100%) |
| Placebo | — | 9/27 (33.3%) | 22/27 (81.5%) |
| Event | Metformin | Placebo |
|---|---|---|
| Exacerbation of asthmaRespiratory, thoracic and mediastinal disorders | 0/26 | 3/27 |
| Severe osmotic symptomsEndocrine disorders | 0/26 | 2/27 |
| Ischaemic heart diseaseCardiac disorders | 1/26 | 0/27 |
| PneumoniaRespiratory, thoracic and mediastinal disorders | 0/26 | 1/27 |
| DiverticulitisGastrointestinal disorders | 0/26 | 1/27 |
| Atypical chest painCardiac disorders | 0/26 | 1/27 |
| Raynaud'sVascular disorders | 0/26 | 1/27 |
| Event | Metformin | Placebo |
|---|---|---|
| OtherGeneral disorders | 10/26 | 18/27 |
| Gastrointestinal side-effectsGastrointestinal disorders | 16/26 | 9/27 |
Heterogeneous but well matched treatment groups
| Age, Continuous(years) | Metformin | Placebo | Total |
|---|---|---|---|
| Mean | 47 ± 15 | 45 ± 15 | 46 ± 15 |
| Sex: Female, Male(Participants) | Metformin | Placebo | Total |
|---|---|---|---|
| Female | 14 | 15 | 29 |
| Male | 12 | 12 | 24 |
| Ethnicity (NIH/OMB)(Participants) | Metformin | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 26 | 27 | 53 |
| Unknown or Not Reported | 0 | 0 | 0 |
| visceral to subcutanous fat ratio(ratio) | Metformin | Placebo | Total |
|---|---|---|---|
| Median | 0.44 (0.33 to 0.67) | 0.58 (0.34 to 0.84) | 0.50 (0.33 to 0.76) |
| HOMA2-IR(HOMA score) | Metformin | Placebo | Total |
|---|---|---|---|
| Median | 4.7 (2.2 to 5.5) | 4.2 (2.8 to 5.4) | 4.4 (2.2 to 5.3) |
Plan to share: No
The record gives a start of Jul 2012, a primary completion of Aug 2014 and a completion of Jan 2015. It does not say whether these dates are actual or estimated.
Results were first posted in Apr 2019, 4 years 8 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jan 2019. You cannot join it, but the record below documents what was studied.
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