Ignite Creation Date:
2025-12-24 @ 6:38 PM
Ignite Modification Date:
2025-12-29 @ 4:57 AM
Study NCT ID:
NCT01799057
Status:
TERMINATED
Last Update Posted:
2016-02-09
First Post:
2013-02-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Effects of Metformin on Functional Capacity in Individuals With Peripheral Artery Disease-Related Intermittent Claudication
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D058729', 'term': 'Peripheral Arterial Disease'}, {'id': 'D007383', 'term': 'Intermittent Claudication'}, {'id': 'D016491', 'term': 'Peripheral Vascular Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D001157', 'term': 'Arterial Occlusive Diseases'}, {'id': 'D050197', 'term': 'Atherosclerosis'}, {'id': 'D007333', 'term': 'Insulin Resistance'}, {'id': 'D009043', 'term': 'Motor Activity'}, {'id': 'D057185', 'term': 'Sedentary Behavior'}], 'ancestors': [{'id': 'D001161', 'term': 'Arteriosclerosis'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D006946', 'term': 'Hyperinsulinism'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D001519', 'term': 'Behavior'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D008687', 'term': 'Metformin'}], 'ancestors': [{'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 2}}, 'statusModule': {'whyStopped': 'The trial has been terminated due to difficulties with recruitment.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2013-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-02', 'completionDateStruct': {'date': '2014-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-02-07', 'studyFirstSubmitDate': '2013-02-22', 'studyFirstSubmitQcDate': '2013-02-22', 'lastUpdatePostDateStruct': {'date': '2016-02-09', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2013-02-26', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Change in glucose uptake and insulin signalling mechanisms in skeletal muscle (exploratory endpoint)', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment'}, {'measure': 'Change in skeletal muscle oxidative capacity and substrate utilization (exploratory endpoint)', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment'}, {'measure': 'Change in inflammation, fibrinolysis and coagulation (exploratory endpoint)', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment'}], 'primaryOutcomes': [{'measure': 'Change in pain-free walking time', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment', 'description': 'Pain-free walking time (time to onset of claudication) will be measured during a graded treadmill exercise test.'}, {'measure': 'Change in maximum walking time', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment', 'description': 'Maximum walking time will be measured during a graded treadmill exercise test.'}], 'secondaryOutcomes': [{'measure': 'Change in questionnaire-based markers of quality of life / perceived functional capacity', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment'}, {'measure': 'Change in endothelial function', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment'}, {'measure': 'Change in skeletal muscle blood flow response to insulin', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment'}, {'measure': 'Change in skeletal muscle blood flow response to acute exercise', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment'}, {'measure': 'Change in insulin sensitivity', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment'}, {'measure': 'Change in objectively measured physical activity / sedentary behaviour in the daily life setting.', 'timeFrame': 'Measured at baseline and following 16-18 weeks treatment'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Peripheral Arterial Disease', 'Intermittent Claudication', 'Peripheral Vascular Diseases', 'Vascular Diseases', 'Cardiovascular Diseases', 'Arterial Occlusive Diseases', 'Atherosclerosis', 'Insulin Resistance', 'Glucose Metabolism', 'Blood Glucose', 'Metformin', 'Biguanides', 'Hypoglycemic Agents', 'Endothelium, Vascular', 'Hemorheology', 'Blood Circulation', 'Regional Blood Flow', 'Microcirculation', 'Exercise', 'Physical Fitness', 'Exercise Test', 'Sedentary Lifestyle', 'Quality of Life', 'Plethysmography'], 'conditions': ['Peripheral Arterial Disease', 'Intermittent Claudication']}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to determine the effects of metformin on functional capacity (pain-free and maximum walking times) in individuals with peripheral artery disease (PAD)-related intermittent claudication.', 'detailedDescription': 'Background and Rationale:\n\nMetformin has demonstrable efficacy in slowing or reversing the progression of various insulin-resistant disease states - most notably type 2 diabetes and pre-diabetes. In seeking to establish proof-of-concept that insulin resistance is a suitable pathophysiological target in the treatment of PAD-related intermittent claudication (pain in the leg muscles during walking, which resolves on exercise cessation), this study will determine whether the known insulin-sensitizing effects of metformin translate to alleviation of the functional limitations imposed by claudication.\n\nStudy Design:\n\nA total of 80 individuals with PAD-related intermittent claudication will be randomised (1:1) to either metformin or matching placebo for 16-18 weeks (double-blind, parallel group design). The maximum daily dose of metformin will be 2000mg (up-titrated from half this dose at 2 weeks if tolerated).\n\nPrimary Hypothesis:\n\nImprovement in functional capacity follows metformin therapy in individuals with PAD-related intermittent claudication. Change in functional capacity will be assessed by the co-primary endpoints of pain-free and maximum walking times during a standard graded treadmill exercise test.\n\nSecondary Aims:\n\nExercise testing for functional performance will be complemented by assessments of perceived physical functioning / quality of life in the daily life setting (using standard questionnaires). As previous studies have indicated cardiovascular effects of metformin incremental to blood glucose-lowering, this study will also investigate potential mechanisms of efficacy relating to the primary endpoints, including changes in endothelial function, blood flow responses to various stimuli (including insulin and acute exercise), insulin sensitivity, and physical activity / sedentary behaviours. Changes in relevant clinical data (including ankle-brachial index and limb hemodynamics by duplex scanning) will also be determined.\n\nOutcomes and Significance:\n\nThe unmet clinical need of efficacious medical therapies for intermittent claudication is a growing problem given the increasing prevalence of PAD worldwide. If positive, this study will identify a new potential treatment that is already widely available. The study will also inform on novel mechanistic targets with relevance to existing and future therapeutic strategies.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '40 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥40 years old.\n* Resting ankle-brachial index (ABI) ≤0.90 in the limiting leg(s), or a \\>20% reduction in the ABI measured immediately post-exercise where the resting ABI is \\>0.90. In cases of incompressible arteries in the limiting leg(s) (i.e. ABI ≥1.40), a toe-brachial index (TBI) of ≤0.70 is required.\n* Peripheral artery stenosis/occlusion in the limiting leg(s), documented by duplex ultrasonography or other imaging tests.\n* Stable (i.e. 3-month history) intermittent claudication in at least one PAD-affected leg.\n* Maximum walking time during graded treadmill exercise testing (Gardner-Skinner protocol) ≥1 minute and ≤16 minutes.\n* Concurrent medications that may affect primary, secondary or exploratory endpoints have remained stable over the previous 3 months.\n* Have given signed informed consent to participate in the study.\n\nExclusion Criteria:\n\n* Identification of any other medical condition requiring immediate therapeutic intervention.\n* Clinically significant abnormal electrocardiogram (ECG) at rest or during exercise that represents a contraindication to study procedures or the study drug.\n* Myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft surgery (CABG), or other major surgery within the previous 6 months.\n* Exercise capacity limited by a factor other than PAD-related intermittent claudication.\n* Any condition that precludes valid completion of a treadmill exercise test.\n* Critical limb ischemia in either leg, defined as PAD-related chronic ischemic rest pain or skin lesions (ulcers, gangrene).\n* Previous peripheral revascularisation or other surgical treatment for PAD in the previous 6 months.\n* Known non-atherosclerotic cause of PAD.\n* Active cancer.\n* Uncontrolled hypertension (resting brachial blood pressure ≥160/100 mmHg).\n* Evidence of pharmacologically-treated or poorly controlled (i.e. HbA1c ≥7.5%) type 2 diabetes or other class of diabetes (e.g. type 1 diabetes).\n* Known intolerance or contraindication(s) to metformin.\n* Known contraindication(s) to "Definity" (perflutren lipid microsphere).\n* Participation or intention to participate in another clinical research study during the study period.\n* History of non-compliance to medical regimens or unwillingness to comply with the study protocol.\n* Any other condition that in the opinion of the Investigators would confound the evaluation and interpretation of the data.\n* Persons directly involved in the execution of the protocol.\n* Incapable of providing written informed consent due to cognitive, language, or other reasons.'}, 'identificationModule': {'nctId': 'NCT01799057', 'briefTitle': 'The Effects of Metformin on Functional Capacity in Individuals With Peripheral Artery Disease-Related Intermittent Claudication', 'organization': {'class': 'OTHER', 'fullName': 'Baker Heart and Diabetes Institute'}, 'officialTitle': 'Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study of Metformin for the Assessment of Changes in Functional Capacity, Endothelial Function, and Hemodynamics in Individuals With Peripheral Artery Disease-Related Intermittent Claudication', 'orgStudyIdInfo': {'id': '493/12'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Metformin', 'description': 'Metformin at a maximum dose of 1000mg twice daily for 16-18 weeks (i.e. maximum of 2000mg per day).', 'interventionNames': ['Drug: Metformin']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Matching placebo twice daily for 16-18 weeks.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Metformin', 'type': 'DRUG', 'otherNames': ['Diaformin'], 'description': 'Participants randomized to metformin will be treated at a maximum dose of 2000mg per day (i.e. 1000mg twice daily for 16-18 weeks; up-titrated from 500mg twice daily for the first 2 weeks). Participants may complete the 16-18 week treatment intervention at the lower dose of 500mg twice daily if limited by side effects.', 'armGroupLabels': ['Metformin']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Participants randomized to placebo will take matching oral capsules according to the same dose schedule specified for the metformin intervention.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '3004', 'city': 'Melbourne', 'state': 'Victoria', 'country': 'Australia', 'facility': 'Baker IDI Heart and Diabetes Institute', 'geoPoint': {'lat': -37.814, 'lon': 144.96332}}], 'overallOfficials': [{'name': 'Bronwyn A Kingwell, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Baker Heart and Diabetes Institute'}, {'name': 'Stephen J Duffy, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Baker Heart and Diabetes Institute'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Baker Heart and Diabetes Institute', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}