Ignite Creation Date:
2024-05-06 @ 3:30 PM
Last Modification Date:
2024-10-26 @ 1:51 PM
Study NCT ID:
NCT04659915
Status:
COMPLETED
Last Update Posted:
2021-09-23
First Post:
2020-12-01
Brief Title:
Counteracting Deleterious Metabolic Glucocorticoid Effects With Metformin
Sponsor:
Eleonora Seelig
Organization:
University Hospital Basel Switzerland
Study Overview
Official Title:
Counteracting Deleterious Metabolic Glucocorticoid Effects With Metformin - A Double-blind Randomized Placebo-controlled Cross-over Study
Status:
COMPLETED
Status Verified Date:
2021-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Gluco-Met
Brief Summary:
Supraphysiological doses of glucocorticoids GCs are widely prescribed as immunosuppressants and metabolic side effects such as obesity and diabetes are extremely common Efforts to investigate and prevent these side effects are lacking The antidiabetic drug metformin was shown in previous studies to prevent deterioration of glucose homeostasis during GC therapy in patients However mechanisms of metformin counteracting GC-induced side effects remain poorly understood
In a randomized placebo-controlled cross-over study 18 healthy volunteers will receive a 7-day course of prednisone with metformin or placebo Established methods will be used to assess systemic changes in energy homeostasis and novel techniques such as metabolomics will identify underlying pathways This will advance the understanding of energy homeostasis during GC excess may prevent thousands of patients from GC-induced side effects and also offers a model for targeting disrupted endogenous GCs secretion
In a randomized placebo-controlled cross-over study 18 healthy volunteers will receive a 7-day course of prednisone with metformin or placebo Established methods will be used to assess systemic changes in energy homeostasis and novel techniques such as metabolomics will identify underlying pathways This will advance the understanding of energy homeostasis during GC excess may prevent thousands of patients from GC-induced side effects and also offers a model for targeting disrupted endogenous GCs secretion
Detailed Description:
Obesity is one of the most serious health problems in the 21st century 1 Currently more than 700 million people world-wide are obese and face an increased risk of morbidity and a reduced life-expectancy of up to 10 years 1 2 High energy food and a sedentary lifestyle are driving the current obesity pandemic 3 Sleep deprivation and psychological stress also have been identified as contributing factors 4 Many of these factors activate the hypothalamic-pituitary-adrenal HPA axis the key regulatory pathway of energy homeostasis Activation of the HPA-axis leads to secretion of glucocorticoids GCs from the adrenal glands GCs control energy homeostasis by mobilizing and redistributing energy substrates 5 In an evolutionary context GCs are particularly important during periods of stress especially when food is scarce In todays environment where food is abundantly available GCs potentially can become deleterious by severely disrupting energy homeostasis Therefore the GC pathway has gained interest as a potential treatment target for the metabolic syndrome
Next to their essential role in energy homeostasis glucocorticoids are the most commonly prescribed immunosuppressant drugs GCs are used for acute as well as chronic conditions in virtually all medical disciplines 6 It is well known that patients on GC treatment are at high risk for developing numerous side effects Next to dyslipidaemia arterial hypertension and cardiovascular disease up to 80 of patients experience weight gain while around 40 develop diabetes 7 Currently no therapies exist to prevent any of these side effects The only available strategy to prevent GC-induced side effects is to restrain GC use
The objective of this project is to test in a clinical study in humans whether metformin can counteract the deleterious metabolic effects developed after a short-term glucocorticoid treatment The primary objective is to test how metformin counteracts metabolic side effects of GCs compared to placebo Secondary objectives are to detect underlying pathways in blood metabolomics adipose tissue gene expression analysis and mitochondria Cytosensor with metformin in combination with prednisone compared to placebo and prednisone
This is a double-blind randomized placebo-controlled cross-over study After screening subjects will be randomized to two crossover 7-day study periods with a washout period of 28 days
A Participants will receive prednisone 30 mgd po and metformin starting with a dose of 500 mgd and increasing the dose by 500 mg every other day until 2000 mgd are achieved
B Participants will receive prednisone 30 mgd po and placebo po starting with a dose of 500 mgd and increasing the dose by 500 mg every other day until 2000 mgd are achieved
Next to their essential role in energy homeostasis glucocorticoids are the most commonly prescribed immunosuppressant drugs GCs are used for acute as well as chronic conditions in virtually all medical disciplines 6 It is well known that patients on GC treatment are at high risk for developing numerous side effects Next to dyslipidaemia arterial hypertension and cardiovascular disease up to 80 of patients experience weight gain while around 40 develop diabetes 7 Currently no therapies exist to prevent any of these side effects The only available strategy to prevent GC-induced side effects is to restrain GC use
The objective of this project is to test in a clinical study in humans whether metformin can counteract the deleterious metabolic effects developed after a short-term glucocorticoid treatment The primary objective is to test how metformin counteracts metabolic side effects of GCs compared to placebo Secondary objectives are to detect underlying pathways in blood metabolomics adipose tissue gene expression analysis and mitochondria Cytosensor with metformin in combination with prednisone compared to placebo and prednisone
This is a double-blind randomized placebo-controlled cross-over study After screening subjects will be randomized to two crossover 7-day study periods with a washout period of 28 days
A Participants will receive prednisone 30 mgd po and metformin starting with a dose of 500 mgd and increasing the dose by 500 mg every other day until 2000 mgd are achieved
B Participants will receive prednisone 30 mgd po and placebo po starting with a dose of 500 mgd and increasing the dose by 500 mg every other day until 2000 mgd are achieved
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None