AzTrials
AzTrials

Peripheral Arterial DiseasePhase 1/2CIPHERNCT06480760

Effects of Carnosine In Patients With Peripheral Arterial Disease Patients

A Phase 1/2 study testing Carnosine in people with Peripheral Arterial Disease, run by Shahid Baba at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 40 to 80 years
Conditions the study is for
Peripheral Arterial Disease
What is being tested?
Carnosine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
144 participants
Where
3 sitesUnited States
Study dates
20 May 2025to 1 Oct 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants between 40-80 years of age.
  • White or African American race.
  • Literate in English.
  • ABI >0.4-<0.90, obtained within 6 weeks from enrollment.
  • Willing and able to comply with protocol requirements.
  • Participant is able to provide informed consent.

Who cannot join

  • 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.
  • Critical limb ischemia with below or above the knee amputations or any form of foot ulceration over the symptomatic leg.
  • Presence of significant injury within 30 days, or vascular intervention on the symptomatic leg within 6 months before enrollment, as per physician's discretion.
  • Participants with a baseline 6MWT of less than 152.0 meters (498ft) or greater than 487.7 meters (1600ft).
  • Known allergy to L-carnosine.
  • Participants with rare autosomal recessive metabolic disorder carnosinemia or carnosinase deficiency.
Show all 13Show fewer
  • Currently participating in other clinical trials.
  • Participation in any carnosine supplementation clinical trial anytime in the past.
  • Participants already taking carnosine.
  • Participants unable to provide urine sample (anuric).
  • Pregnant participants.
  • Participants using dual antiplatelet therapies will not be included for biopsy.
  • Participants with internal metallic objects in body will not be eligible for MRI or 1HMRS.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Shahid Baba, PhD contact

502-296-7713

shahid.baba@louisville.edu

Amit Dwivedi, MD contact

502-583-8303

amit.dwivedi@louisville.edu

United States3 sites, 3 recruiting

  • University of Louisville School of Medicine, Department of Medicine, Division of Environmental Medicine

    Louisville, Kentucky, 40202

    Shahid Baba, PhD, 502-296-7713, shahid.baba@louisville.edu

    Amit Dwivedi, MD, 502-583-8303, amit.dwivedi@louisville.edu

    Recruiting

  • University Surgical Associates, 401 E. Chestnut St, Suite 710

    Louisville, Kentucky, 40202

    Shahid Baba, PhD, 502-296-7713, shahid.baba@louisville.edu

    Amit Dwivedi, MD, 502-583-8303, amit.dwivedi@louisville.edu

    Not yet recruiting

  • UofL Physicians - Vascular Surgery Associates, 201 Abraham Flexner Way, Suite 1004

    Louisville, Kentucky, 40202

    Shahid Baba, PhD, 502-296-7713, shahid.baba@louisville.edu

    Amit Dwivedi, MD, 502-583-8303, amit.dwivedi@louisville.edu

    Not yet recruiting

Other trials in United States

About this study

Official title: Effects of Carnosine In Patients With Peripheral Arterial Disease Patients; Randomized Intervention Trial (CIPHER)

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.

Read the detailed description

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.

Being tested
Carnosine
Keywords
peripheral arterial disease, carnosine
Medical subject headings
Peripheral Arterial Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarnosineDrug

    Food ingredient (supplement)

Study groups in NCT06480760
Study groupRoleWhat they receive
PlaceboNo interventionCellulose
CarnosineExperimentalCarnosine 2 g daily for 6 months
Receives: Drug: Carnosine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Measure distance covered on six-minute walk test (6MWT)

    Distance covered on a flat and hard surface in 6 minutes. Units: Feet

    Measured: Baseline, 3 months, 6 months, 9 months

Secondary outcomes (19)

  1. Measure Ankle-Brachial Index (ABI)

    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

    Measured: Baseline, 3 months, 6 months, 9 months

  2. Treadmill Testing

    Graded treadmill testing using the Gardener protocol until the onset of the maximal claudication pain.

    Units: Meters

    Measured: Baseline, 3 months, 6 months

  3. Skin Integrity

    Check the color, trophic changes and flakes. Units: None

    Measured: Baseline, 3 months, 6 months

  4. Musculoskeletal Assessment

    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.

    Units: Visual analog scale (VAS 0-10); 0-10 corresponds to the no pain to severe pain.

    Measured: Baseline, 3 months, 6 months

  5. Neuromuscular Assessment

    For neuromuscular assessment assess the sharp-dull and deep pressure sensation. Units: None

    Measured: Baseline, 3 months, 6 months

  6. Balance Assessment

    Balance assessment will be measured by Berg balance assessment. Units: Scale 0 to 4, with 4 indicating normal and 0 representing severe impairment

    Measured: Baseline, 3 months, 6 months

  7. Quality of life Questionnaire

    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.

    Measured: Baseline, 3 months, 6 months, 9 months

  8. Assessment of PAD Severity

    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)

    Measures: (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.

    Measured: Baseline, 3 months, 6 months, 9 months

  9. Depressive Symptoms Questionnaire

    Depression symptoms will be evaluated using Patient Health Questionnaire-9 (PHQ-9).

    Units: 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.

    Measured: Baseline, 3 months, 6 months, 9 months

  10. 24-hour Dietary Recall

    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.

    Measured: Baseline, 3 months, 6 months, 9 months

  11. Daily Walking Ability

    Steps over a period of 6 days using triaxial pedometer. Units: step counts

    Measured: -7-Baseline, Day 90-97, Day 180-187, Day 270-277

  12. Blood Collection and Analysis

    White blood cells, red blood cells. Units: Cells per cubic millimeter. Neutrophils, lymphocytes, monocytes, eosinophils, basophils. Units: percent

    Measured: Baseline, 3 months, 6 months, 9 months

  13. Blood Collection and Analysis

    Sodium, phosphate, chloride, calcium, glucose, creatinine, albumin, ALT and AST Units: mg/dL

    Measured: Baseline, 3 months, 6 months, 9 months

  14. Measurement of Carnosine in Blood and Urine

    Using mass spectrometry will measure carnosine bioavailability. Units: moles

    Measured: Baseline, 3 months, 6 months, 9 months

  15. Measure Angiogenic Cell Population

    Flow cytometry: measure angiogenic cell population. Units: Number of cells

    Measured: Baseline, 3 months, 6 months, 9 months

  16. Mitochondrial Abundance Measurements

    Perform RTPCR to measure expression of different mitochondrial genes. Units: Relative mRNA expression

    Measured: Baseline, 3 months, 6 months, 9 months

  17. Measurement of Carnosine in Muscle

    Using magnetic resonance spectroscopy, will measure carnosine accumulation before and after supplementation.

    Units: millimole.

    Measured: Baseline, 6 months

  18. Measurement of Blood Flow

    Using magnetic resonance imaging will measure blood flow in the legs. Units: mL/min

    Measured: Baseline, 6 months

  19. Calf Muscle Biopsy

    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.

    Measured: Baseline, 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jun 2024
  2. Study start20 May 2025
  3. Primary completion1 Oct 2028 (estimated)
  4. Study completion1 Oct 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
A randomized, double-blinded longitudinal study in approximately 144 PAD patients
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
144 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06480760
Sponsor's protocol ID
24.0309
Other IDs
R01HL163419
Acronym
CIPHER
Status last verified
May 2025
First submitted
24 Jun 2024
Last updated
29 May 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 27040154

  • 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.

    PubMed 11056102

  • 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.

    PubMed 7867189

  • 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. Circ Res. 2005 Mar 18;96(5):576-82. doi: 10.1161/01.RES.0000159389.55544.20. Epub 2005 Feb 17.

    PubMed 15718500

  • Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003 Jun 23;161(6):1163-77. doi: 10.1083/jcb.200302047. Epub 2003 Jun 16.

    PubMed 12810700

  • Creager MA, Olin JW, Belch JJ, Moneta GL, Henry TD, Rajagopalan S, Annex BH, Hiatt WR. Effect of hypoxia-inducible factor-1alpha gene therapy on walking performance in patients with intermittent claudication. Circulation. 2011 Oct 18;124(16):1765-73. doi: 10.1161/CIRCULATIONAHA.110.009407. Epub 2011 Sep 26.

    PubMed 21947297

  • Wang GL, Semenza GL. Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction. Blood. 1993 Dec 15;82(12):3610-5.

    PubMed 8260699

  • Silvestre JS, Mallat Z, Tedgui A, Levy BI. Post-ischaemic neovascularization and inflammation. Cardiovasc Res. 2008 May 1;78(2):242-9. doi: 10.1093/cvr/cvn027. Epub 2008 Feb 5.

    PubMed 18252762

  • Aicher A, Zeiher AM, Dimmeler S. Mobilizing endothelial progenitor cells. Hypertension. 2005 Mar;45(3):321-5. doi: 10.1161/01.HYP.0000154789.28695.ea. Epub 2005 Jan 17.

    PubMed 15655116

  • Asahara T, Takahashi T, Masuda H, Kalka C, Chen D, Iwaguro H, Inai Y, Silver M, Isner JM. VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J. 1999 Jul 15;18(14):3964-72. doi: 10.1093/emboj/18.14.3964.

    PubMed 10406801

  • Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL. Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996 Sep;16(9):4604-13. doi: 10.1128/MCB.16.9.4604.

    PubMed 8756616

  • Ziello JE, Jovin IS, Huang Y. Hypoxia-Inducible Factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J Biol Med. 2007 Jun;80(2):51-60.

    PubMed 18160990

  • Heil M, Schaper W. Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circ Res. 2004 Sep 3;95(5):449-58. doi: 10.1161/01.RES.0000141145.78900.44.

    PubMed 15345667

  • Serrano Hernando FJ, Martin Conejero A. [Peripheral artery disease: pathophysiology, diagnosis and treatment]. Rev Esp Cardiol. 2007 Sep;60(9):969-82. doi: 10.1157/13109651. Spanish.

    PubMed 17915154

  • Chez MG, Buchanan CP, Aimonovitch MC, Becker M, Schaefer K, Black C, Komen J. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol. 2002 Nov;17(11):833-7. doi: 10.1177/08830738020170111501.

    PubMed 12585724

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carnosine in people with Peripheral Arterial Disease, run by Shahid Baba at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Shahid Baba, PhD (502-296-7713, shahid.baba@louisville.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measure distance covered on six-minute walk test (6MWT) (time frame: Baseline, 3 months, 6 months, 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06480760, which also lists 39 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in