Ignite Creation Date:
2025-12-25 @ 2:01 AM
Ignite Modification Date:
2026-02-22 @ 7:03 PM
Study NCT ID:
NCT06480760
Status:
RECRUITING
Last Update Posted:
2025-05-29
First Post:
2024-06-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Effects of Carnosine In Patients With Peripheral Arterial Disease Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D058729', 'term': 'Peripheral Arterial Disease'}], 'ancestors': [{'id': 'D050197', 'term': 'Atherosclerosis'}, {'id': 'D001161', 'term': 'Arteriosclerosis'}, {'id': 'D001157', 'term': 'Arterial Occlusive Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D016491', 'term': 'Peripheral Vascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D002336', 'term': 'Carnosine'}], 'ancestors': [{'id': 'D009479', 'term': 'Neuropeptides'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D004151', 'term': 'Dipeptides'}, {'id': 'D009842', 'term': 'Oligopeptides'}, {'id': 'D009419', 'term': 'Nerve Tissue Proteins'}, {'id': 'D011506', 'term': 'Proteins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'A randomized, double-blinded longitudinal study in approximately 144 PAD patients'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 144}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-05-20', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-05', 'completionDateStruct': {'date': '2028-10-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-05-22', 'studyFirstSubmitDate': '2024-06-24', 'studyFirstSubmitQcDate': '2024-06-24', 'lastUpdatePostDateStruct': {'date': '2025-05-29', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-06-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-10-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Measure distance covered on six-minute walk test (6MWT)', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': 'Distance covered on a flat and hard surface in 6 minutes. Units: Feet'}], 'secondaryOutcomes': [{'measure': 'Measure Ankle-Brachial Index (ABI)', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': 'Ratio of blood pressure measurements from the arms and ankles. Units: Normal range 1.0-1.4 and lower than 0.9 is an indication of peripheral arterial disease'}, {'measure': 'Treadmill Testing', 'timeFrame': 'Baseline, 3 months, 6 months', 'description': 'Graded treadmill testing using the Gardener protocol until the onset of the maximal claudication pain.\n\nUnits: Meters'}, {'measure': 'Skin Integrity', 'timeFrame': 'Baseline, 3 months, 6 months', 'description': 'Check the color, trophic changes and flakes. Units: None'}, {'measure': 'Musculoskeletal Assessment', 'timeFrame': 'Baseline, 3 months, 6 months', 'description': 'Perform goniometric measurements, assess pain and conduct muscle strength testing. Upper limb muscle strength will be evaluated by hand-grip test and lower limb muscle strength will be evaluated by using a dynamometer.\n\nUnits: Visual analog scale (VAS 0-10); 0-10 corresponds to the no pain to severe pain.'}, {'measure': 'Neuromuscular Assessment', 'timeFrame': 'Baseline, 3 months, 6 months', 'description': 'For neuromuscular assessment assess the sharp-dull and deep pressure sensation. Units: None'}, {'measure': 'Balance Assessment', 'timeFrame': 'Baseline, 3 months, 6 months', 'description': 'Balance assessment will be measured by Berg balance assessment. Units: Scale 0 to 4, with 4 indicating normal and 0 representing severe impairment'}, {'measure': 'Quality of life Questionnaire', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': 'Health related quality of life using a Short-Form 36 general health survey. Units: An arbitrary scale 0 to 100, with higher scores representing better health.'}, {'measure': 'Assessment of PAD Severity', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': 'To assess the leg symptoms, participants who are affirmative for the pain in legs or buttock on walking will be characterized by the responses to San Diego Claudication Questionnaire (SDCQ) and Walking Impairment Questionnaire (WIQ)\n\nMeasures: (1) intermittent claudication, (2) leg pain on exertion and rest, (3) atypical exertional leg pain, (4) atypical exertional leg pain/stop, and (5) no exertional pain.'}, {'measure': 'Depressive Symptoms Questionnaire', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': 'Depression symptoms will be evaluated using Patient Health Questionnaire-9 (PHQ-9).\n\nUnits: Scores evaluated on a 4-point scale from "not at all" to "nearly every day". PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression respectively.'}, {'measure': '24-hour Dietary Recall', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': "Recall of participant's dietary patterns over the past 24 hours from the time of the visit using web-based, Automated Self-Administered 24-hour (ASA24®) Dietary Assessment Tool 2024 Version."}, {'measure': 'Daily Walking Ability', 'timeFrame': '-7-Baseline, Day 90-97, Day 180-187, Day 270-277', 'description': 'Steps over a period of 6 days using triaxial pedometer. Units: step counts'}, {'measure': 'Blood Collection and Analysis', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': 'White blood cells, red blood cells. Units: Cells per cubic millimeter. Neutrophils, lymphocytes, monocytes, eosinophils, basophils. Units: percent'}, {'measure': 'Blood Collection and Analysis', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': 'Sodium, phosphate, chloride, calcium, glucose, creatinine, albumin, ALT and AST Units: mg/dL'}, {'measure': 'Measurement of Carnosine in Blood and Urine', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': 'Using mass spectrometry will measure carnosine bioavailability. Units: moles'}, {'measure': 'Measure Angiogenic Cell Population', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': 'Flow cytometry: measure angiogenic cell population. Units: Number of cells'}, {'measure': 'Mitochondrial Abundance Measurements', 'timeFrame': 'Baseline, 3 months, 6 months, 9 months', 'description': 'Perform RTPCR to measure expression of different mitochondrial genes. Units: Relative mRNA expression'}, {'measure': 'Measurement of Carnosine in Muscle', 'timeFrame': 'Baseline, 6 months', 'description': 'Using magnetic resonance spectroscopy, will measure carnosine accumulation before and after supplementation.\n\nUnits: millimole.'}, {'measure': 'Measurement of Blood Flow', 'timeFrame': 'Baseline, 6 months', 'description': 'Using magnetic resonance imaging will measure blood flow in the legs. Units: mL/min'}, {'measure': 'Calf Muscle Biopsy', 'timeFrame': 'Baseline, 6 months', 'description': 'Optional muscle biopsy will be obtained by a trained vascular surgeon from the consistent location of medial gastrocnemius of the symptomatic leg using a ¼ inch bore percutaneous biopsy needle.'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['peripheral arterial disease', 'carnosine'], 'conditions': ['Peripheral Arterial Disease']}, 'referencesModule': {'references': [{'pmid': '27040154', 'type': 'BACKGROUND', 'citation': 'de Courten B, Jakubova M, de Courten MP, Kukurova IJ, Vallova S, Krumpolec P, Valkovic L, Kurdiova T, Garzon D, Barbaresi S, Teede HJ, Derave W, Krssak M, Aldini G, Ukropec J, Ukropcova B. Effects of carnosine supplementation on glucose metabolism: Pilot clinical trial. Obesity (Silver Spring). 2016 May;24(5):1027-34. doi: 10.1002/oby.21434. Epub 2016 Apr 4.'}, {'pmid': '11056102', 'type': 'BACKGROUND', 'citation': 'Vincent KA, Shyu KG, Luo Y, Magner M, Tio RA, Jiang C, Goldberg MA, Akita GY, Gregory RJ, Isner JM. Angiogenesis is induced in a rabbit model of hindlimb ischemia by naked DNA encoding an HIF-1alpha/VP16 hybrid transcription factor. Circulation. 2000 Oct 31;102(18):2255-61. doi: 10.1161/01.cir.102.18.2255.'}, {'pmid': '7867189', 'type': 'BACKGROUND', 'citation': 'Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study. Circulation. 1995 Mar 1;91(5):1472-9. doi: 10.1161/01.cir.91.5.1472.'}, {'pmid': '15718500', 'type': 'BACKGROUND', 'citation': 'Waeckel L, Mallat Z, Potteaux S, Combadiere C, Clergue M, Duriez M, Bao L, Gerard C, Rollins BJ, Tedgui A, Levy BI, Silvestre JS. Impairment in postischemic neovascularization in mice lacking the CXC chemokine receptor 3. 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Epub 2010 Dec 15.'}, {'pmid': '31312142', 'type': 'BACKGROUND', 'citation': 'Boakye AA, Zhang D, Guo L, Zheng Y, Hoetker D, Zhao J, Posa DK, Ng CK, Zheng H, Kumar A, Kumar V, Wempe MF, Bhatnagar A, Conklin DJ, Baba SP. Carnosine Supplementation Enhances Post Ischemic Hind Limb Revascularization. Front Physiol. 2019 Jul 2;10:751. doi: 10.3389/fphys.2019.00751. eCollection 2019.'}, {'pmid': '36545878', 'type': 'BACKGROUND', 'citation': 'Schon M, Just I, Krumpolec P, Blazicek P, Valkovic L, Aldini G, Tsai CL, De Courten B, Krssak M, Ukropcova B, Ukropec J. Supplementation-induced change in muscle carnosine is paralleled by changes in muscle metabolism, protein glycation and reactive carbonyl species sequestering. Physiol Res. 2023 Mar 8;72(1):87-97. doi: 10.33549/physiolres.934911. Epub 2022 Dec 22.'}, {'pmid': '22852051', 'type': 'BACKGROUND', 'citation': 'Caruso J, Charles J, Unruh K, Giebel R, Learmonth L, Potter W. Ergogenic effects of beta-alanine and carnosine: proposed future research to quantify their efficacy. Nutrients. 2012 Jul;4(7):585-601. doi: 10.3390/nu4070585. Epub 2012 Jun 26.'}, {'pmid': '23899755', 'type': 'BACKGROUND', 'citation': 'Harris RC, Stellingwerff T. Effect of beta-alanine supplementation on high-intensity exercise performance. Nestle Nutr Inst Workshop Ser. 2013;76:61-71. doi: 10.1159/000350258. Epub 2013 Jul 25.'}, {'pmid': '22020113', 'type': 'BACKGROUND', 'citation': 'Hipkiss AR. Energy metabolism, proteotoxic stress and age-related dysfunction - protection by carnosine. Mol Aspects Med. 2011 Aug;32(4-6):267-78. doi: 10.1016/j.mam.2011.10.004. Epub 2011 Oct 15.'}, {'pmid': '12473676', 'type': 'BACKGROUND', 'citation': 'Teufel M, Saudek V, Ledig JP, Bernhardt A, Boularand S, Carreau A, Cairns NJ, Carter C, Cowley DJ, Duverger D, Ganzhorn AJ, Guenet C, Heintzelmann B, Laucher V, Sauvage C, Smirnova T. Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. J Biol Chem. 2003 Feb 21;278(8):6521-31. doi: 10.1074/jbc.M209764200. Epub 2002 Dec 6.'}, {'pmid': '20097752', 'type': 'BACKGROUND', 'citation': 'Drozak J, Veiga-da-Cunha M, Vertommen D, Stroobant V, Van Schaftingen E. Molecular identification of carnosine synthase as ATP-grasp domain-containing protein 1 (ATPGD1). J Biol Chem. 2010 Mar 26;285(13):9346-9356. doi: 10.1074/jbc.M109.095505. Epub 2010 Jan 22.'}, {'pmid': '25287762', 'type': 'BACKGROUND', 'citation': 'Lombardi C, Carubelli V, Lazzarini V, Vizzardi E, Bordonali T, Ciccarese C, Castrini AI, Dei Cas A, Nodari S, Metra M. Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure. Nutrition. 2015 Jan;31(1):72-8. doi: 10.1016/j.nut.2014.04.021. Epub 2014 May 10.'}, {'pmid': '25908725', 'type': 'BACKGROUND', 'citation': 'Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res. 2015 Apr 24;116(9):1509-26. doi: 10.1161/CIRCRESAHA.116.303849.'}, {'pmid': '23670612', 'type': 'BACKGROUND', 'citation': 'Annex BH. Therapeutic angiogenesis for critical limb ischaemia. Nat Rev Cardiol. 2013 Jul;10(7):387-96. doi: 10.1038/nrcardio.2013.70. Epub 2013 May 14.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to determine whether carnosine (a food ingredient found in chicken and red meat) supplementation (2 g) for 6 months in participants with non-claudication and claudication peripheral arterial disease (PAD) improves walking ability. Previous studies with heart failure patients have shown that carnosine supplementation increases walking capacity in these patients.', 'detailedDescription': 'The objective of this double-blinded longitudinal study is to determine whether carnosine supplementation (2 g) for 6 months in participants with non-claudication and claudication peripheral arterial disease (PAD) improves walking ability. In this pilot study we will enroll 144 participants that will be divided into placebo (n=72) and carnosine groups (n=72). We will measure the distance covered on the 6-minute walk test (6-MWT) and the pain free walking capacity on the treadmill before and after the placebo or carnosine supplementation. We will measure ankle branchial index (ABI) and blood flow by magnetic resonance imaging (MRI) before and after the carnosine and placebo supplementation. In addition, we will measure carnosine by 1HMRS (Proton magnetic resonance spectroscopy), perform, global metabolomics and proteomics in the skeletal muscle, a comprehensive lipid and metabolic profile of blood, uptake of carnosine in red blood cells (RBCs), and measure carnosine aldehyde conjugates in the urine before and after 6 months of carnosine and placebo supplementation. Following completion of the study, we will follow the participants for another 3 months and examine the durability of carnosine supplementation.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '40 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Participants between 40-80 years of age.\n2. White or African American race.\n3. Literate in English.\n4. ABI \\>0.4-\\<0.90, obtained within 6 weeks from enrollment.\n5. Willing and able to comply with protocol requirements.\n6. Participant is able to provide informed consent.\n\nExclusion Criteria:\n\n1. As per physician's discretion, participants with HIV, hepatitis, significant liver disease, anemia, renal disease requiring dialysis, lung disease requiring home oxygen therapy, and active cancer may be excluded.\n2. Critical limb ischemia with below or above the knee amputations or any form of foot ulceration over the symptomatic leg.\n3. Presence of significant injury within 30 days, or vascular intervention on the symptomatic leg within 6 months before enrollment, as per physician's discretion.\n4. Participants with a baseline 6MWT of less than 152.0 meters (498ft) or greater than 487.7 meters (1600ft).\n5. Known allergy to L-carnosine.\n6. Participants with rare autosomal recessive metabolic disorder carnosinemia or carnosinase deficiency.\n7. Currently participating in other clinical trials.\n8. Participation in any carnosine supplementation clinical trial anytime in the past.\n9. Participants already taking carnosine.\n10. Participants unable to provide urine sample (anuric).\n11. Pregnant participants.\n12. Participants using dual antiplatelet therapies will not be included for biopsy.\n13. Participants with internal metallic objects in body will not be eligible for MRI or 1HMRS."}, 'identificationModule': {'nctId': 'NCT06480760', 'acronym': 'CIPHER', 'briefTitle': 'Effects of Carnosine In Patients With Peripheral Arterial Disease Patients', 'organization': {'class': 'OTHER', 'fullName': 'University of Louisville'}, 'officialTitle': 'Effects of Carnosine In Patients With Peripheral Arterial Disease Patients; Randomized Intervention Trial (CIPHER)', 'orgStudyIdInfo': {'id': '24.0309'}, 'secondaryIdInfos': [{'id': 'R01HL163419', 'link': 'https://reporter.nih.gov/quickSearch/R01HL163419', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'NO_INTERVENTION', 'label': 'Placebo', 'description': 'Cellulose'}, {'type': 'EXPERIMENTAL', 'label': 'Carnosine', 'description': 'Carnosine 2 g daily for 6 months', 'interventionNames': ['Drug: Carnosine']}], 'interventions': [{'name': 'Carnosine', 'type': 'DRUG', 'description': 'Food ingredient (supplement)', 'armGroupLabels': ['Carnosine']}]}, 'contactsLocationsModule': {'locations': [{'zip': '40202', 'city': 'Louisville', 'state': 'Kentucky', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Shahid Baba, PhD', 'role': 'CONTACT', 'email': 'shahid.baba@louisville.edu', 'phone': '502-296-7713'}, {'name': 'Amit Dwivedi, MD', 'role': 'CONTACT', 'email': 'amit.dwivedi@louisville.edu', 'phone': '502-583-8303'}], 'facility': 'University of Louisville School of Medicine, Department of Medicine, Division of Environmental Medicine', 'geoPoint': {'lat': 38.25424, 'lon': -85.75941}}, {'zip': '40202', 'city': 'Louisville', 'state': 'Kentucky', 'status': 'NOT_YET_RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Shahid Baba, PhD', 'role': 'CONTACT', 'email': 'shahid.baba@louisville.edu', 'phone': '502-296-7713'}, {'name': 'Amit Dwivedi, MD', 'role': 'CONTACT', 'email': 'amit.dwivedi@louisville.edu', 'phone': '502-583-8303'}], 'facility': 'University Surgical Associates, 401 E. Chestnut St, Suite 710', 'geoPoint': {'lat': 38.25424, 'lon': -85.75941}}, {'zip': '40202', 'city': 'Louisville', 'state': 'Kentucky', 'status': 'NOT_YET_RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Shahid Baba, PhD', 'role': 'CONTACT', 'email': 'shahid.baba@louisville.edu', 'phone': '502-296-7713'}, {'name': 'Amit Dwivedi, MD', 'role': 'CONTACT', 'email': 'amit.dwivedi@louisville.edu', 'phone': '502-583-8303'}], 'facility': 'UofL Physicians - Vascular Surgery Associates, 201 Abraham Flexner Way, Suite 1004', 'geoPoint': {'lat': 38.25424, 'lon': -85.75941}}], 'centralContacts': [{'name': 'Shahid Baba, PhD', 'role': 'CONTACT', 'email': 'shahid.baba@louisville.edu', 'phone': '502-296-7713'}, {'name': 'Amit Dwivedi, MD', 'role': 'CONTACT', 'email': 'amit.dwivedi@louisville.edu', 'phone': '502-583-8303'}], 'overallOfficials': [{'name': 'Shahid Baba, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Louisville School of Medicine'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Shahid Baba', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institutes of Health (NIH)', 'class': 'NIH'}, {'name': 'National Heart, Lung, and Blood Institute (NHLBI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Shahid Baba', 'investigatorAffiliation': 'University of Louisville'}}}}