Metformin Therapy in Non-diabetic AAA Patients (MetAAA)
Primary Purpose
Abdominal Aortic Aneurysm
Status
Enrolling by invitation
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
Metformin Glucophage 500mg (IR) tablets M90
Placebo Oral Tablet
Sponsored by
About this trial
This is an interventional treatment trial for Abdominal Aortic Aneurysm focused on measuring abdominal aortic aneurysm, metformin, non-diabetic, placebo
Eligibility Criteria
Inclusion Criteria:
• Infrarenal AAA of 3-4.9 cm maximum diameter
Exclusion Criteria:
- premenopausal female patients with a pregnancy possibility
- patients with diabetes
- indication for surgical AAA repair
- contraindications for metformin, i.e. severly reduced kidney function (eGFR <30 ml/min), liver dysfunction, pancreatitis, alcohol abusus, malnutrition and decompensated heart failure
Sites / Locations
- Medical University of Vienna, Department of Surgery, Division of Vascular Surgery
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
INVESTIGATIONAL DRUG
COMPARATIVE DRUG
Arm Description
oral metformin treatment with 2000Mg daily: Glucophage 500mg Tablet (2-0-2) daily for 1 year
Placebo matching M90 Oral Tablet treatment twice daily (2-0-2) for 1 year
Outcomes
Primary Outcome Measures
AAA growth over 12 months in mm
AAA maximum diameter in CT scan
Secondary Outcome Measures
inflammation markers IL-6
inflammatory cytokines and parameters of neutrophil activation in patient plasma
glucose markers insulin and glucose
inflammatory cytokines and parameters of neutrophil activation in patient plasma
neutrophil markers NGAL
inflammatory cytokines and parameters of neutrophil activation in patient plasma
ineutrophil marker MPO
inflammatory cytokines and parameters of neutrophil activation in patient plasma
neutrophil marker elastase
inflammatory cytokines and parameters of neutrophil activation in patient plasma
AAA thrombus
volume of AAA thrombus
Full Information
NCT ID
NCT03507413
First Posted
March 29, 2018
Last Updated
August 28, 2022
Sponsor
Medical University of Vienna
Collaborators
Merck Serono GmbH, Germany
1. Study Identification
Unique Protocol Identification Number
NCT03507413
Brief Title
Metformin Therapy in Non-diabetic AAA Patients
Acronym
MetAAA
Official Title
A Prospective Randomized, Double Blind, Placebo-controlled, Safety and Efficacy Study of Metformin as add-on Therapy in Non-diabetic Patients With Abdominal Aortic Aneurysm (MetAAA Study)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Enrolling by invitation
Study Start Date
September 26, 2018 (Actual)
Primary Completion Date
October 15, 2022 (Anticipated)
Study Completion Date
November 15, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna
Collaborators
Merck Serono GmbH, Germany
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A prospective randomized, double blind, placebo-controlled, safety and efficacy study of metformin as add-on therapy in abdominal aortic aneurysm (AAA)
OBJECTIVES Primary Objective
To demonstrate treatment efficacy of metformin in AAA in comparison to placebo or active comparator, as measured by growth of the AAA maximum diameter at 12 months Secondary Objectives
To asses inflammatory cytokines and parameters of neutrophil activation in AAA in response to metformin treatment by glucose
insulin
Interleukin-6
markers of neutrophil activation (MPO, elastase, NGAL)
Detailed Description
DESIGN / PHASE Prospective, single-center, randomized, parallel group, double-blind, placebo controlled, phase IIa study STUDY PLANNED DURATION First patient First visit Year 1 1Q
Last patient First visit Year 2 4Q Last patient Last visit Year 3 2Q
CENTER(S)
COUNTRY(IES) 1 center in 1 country Austria PATIENTS / GROUPS 170 patients in 2 groups 85 patients per group Randomization ratio 1:1 Stratification for hypertension, age, smoking habit, sex INCLUSION CRITERIA
Infrarenal AAA of 3.0-4.9 cm maximum diameter EXCLUSION CRITERIA
premenopausal female patients with a pregnancy possibility
patients with diabetes
indication for surgical AAA repair
life expectancy <2 years
contraindications for metformin, i.e. severely reduced kidney function (eGFR <30 ml/min), liver dysfunction, pancreatitis, alcohol abuse, malnutrition and decompensated heart failure STUDY PERIODS
1-2 year recruitment
1 year treatment
12 month follow-up INVESTIGATIONAL DRUG
Metformin:
initial dose: 500 mg 1-0-1 target dose: 1000 mg 1-0-1 COMPARATIVE DRUG /CONTROL CONDITION Placebo Initial and target dose: tablets 1-0-1 CONCOMITANT MEDICATION Allowed (standard of care) EFFICACY ENDPOINTS AAA growth (in maximum diameter) over 1 year TOLERABILITY / SAFETY surgery when AAA>5.5 cm for men, > 5 cm for women
Metformin Therapy for AAA Department of Surgery, Division of Vascular Surgery Medical University of Vienna, Austria
ENDPOINTS
adverse drug reactions liver insufficiency sustained reduction of kidney function with glomeral filtration rate <30 mg/dl (upon temporary renal insufficiency, infections, exsiccosis, diarrhea and lactic acidosis, metformin treatment will only be paused)
PHARMACOKINETIC / PHARMACODYNAMIC ENDPOINTS
glucose
insulin
Interleukin-6
markers of neutrophil activation (MPO, elastase, NGAL)
QUALITY OF LIFE / PHARMACOECONOMIC ENDPOINTS gastrointestinal discomfort (as assessed in the initial drop-out phase for patient exclusion)
STATISTICAL METHODOLOGY Primary Endpoint AAA growth at 12 months in mm
Null and alternative hypotheses:
H0: Metformin does not reduce AAA growth
H1: Metformin reduces AAA growth from mean 1.7 to 0.4 mm per year Type-I and -II errors:
Significance: 5% Power: 80% 1.7±3.3 mm (mean±SD) without Metformin and 0.4±2.3 mm (mean±SD) with Metformin treatment Sample size calculation 77 per group plus 16 patients drop out Total N= 170 Statistical methodology Main analysis set: per protocol Primary endpoint: analysis of covariance adjusted for baseline AAA diameter Pharmacokinetic endpoints: analysis of covariance adjusted for baseline value. Parametric assumptions will be graphically checked with histograms.
In case of non-normal distributions analysis of covariance will be performed after a logarithmic or rank transformation.
Safety endpoints will be described by cumulative incidence curves
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Abdominal Aortic Aneurysm
Keywords
abdominal aortic aneurysm, metformin, non-diabetic, placebo
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
prospective, randomized, double blind, placebo-controlled, safety and efficacy study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
170 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
INVESTIGATIONAL DRUG
Arm Type
Active Comparator
Arm Description
oral metformin treatment with 2000Mg daily: Glucophage 500mg Tablet (2-0-2) daily for 1 year
Arm Title
COMPARATIVE DRUG
Arm Type
Placebo Comparator
Arm Description
Placebo matching M90 Oral Tablet treatment twice daily (2-0-2) for 1 year
Intervention Type
Drug
Intervention Name(s)
Metformin Glucophage 500mg (IR) tablets M90
Other Intervention Name(s)
Glucophage (Merck)
Intervention Description
oral metformin Glucophage treatment 500 mg daily (2-0-2) for 1 year
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Other Intervention Name(s)
Placebo (Merck)
Intervention Description
Placebo Oral Tablet M90 treatment twice daily (2-0-2) for 1 year
Primary Outcome Measure Information:
Title
AAA growth over 12 months in mm
Description
AAA maximum diameter in CT scan
Time Frame
12 months
Secondary Outcome Measure Information:
Title
inflammation markers IL-6
Description
inflammatory cytokines and parameters of neutrophil activation in patient plasma
Time Frame
12 months
Title
glucose markers insulin and glucose
Description
inflammatory cytokines and parameters of neutrophil activation in patient plasma
Time Frame
12 months
Title
neutrophil markers NGAL
Description
inflammatory cytokines and parameters of neutrophil activation in patient plasma
Time Frame
12 months
Title
ineutrophil marker MPO
Description
inflammatory cytokines and parameters of neutrophil activation in patient plasma
Time Frame
12 months
Title
neutrophil marker elastase
Description
inflammatory cytokines and parameters of neutrophil activation in patient plasma
Time Frame
12 months
Title
AAA thrombus
Description
volume of AAA thrombus
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
• Infrarenal AAA of 3-4.9 cm maximum diameter
Exclusion Criteria:
premenopausal female patients with a pregnancy possibility
patients with diabetes
indication for surgical AAA repair
contraindications for metformin, i.e. severly reduced kidney function (eGFR <30 ml/min), liver dysfunction, pancreatitis, alcohol abusus, malnutrition and decompensated heart failure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christoph Neumayer, MD
Organizational Affiliation
Medical University of Vienna
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wolf-Hans Eilenberg, MD, PhD
Organizational Affiliation
Medical University of Vienna
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Vienna, Department of Surgery, Division of Vascular Surgery
City
Vienna
ZIP/Postal Code
1090
Country
Austria
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
Citation
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Results Reference
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Metformin Therapy in Non-diabetic AAA Patients
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