Efficacy Study of Oral L-Citrulline in Patients Taking Simvastatin With Peripheral Arterial Disease

October 17, 2006 updated by: Angiogenix

Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Oral L-Citrulline Compared to Placebo in Patients Taking Background Simvastatin 40 mg qD and With Peripheral Arterial Disease Including Intermittent Claudication

To prove the combination of L-citrulline with simvastatin leads to greater improvement in the symptoms of peripheral arterial disease (PAD) than simvastatin alone by evaluating oral L- citrulline or placebo against simvastatin for improvement in treadmill walking distance in patients, 40-75 years of age, who have PAD with intermittent claudication.

Study Overview

Detailed Description

The primary objective of this study is to prove the combination of L-citrulline with simvastatin leads to greater improvement in the symptoms of PAD than simvastatin alone. This will be accomplished by evaluating efficacy of orally administered L-citrulline or placebo against background therapy with simvastatin for improvement in treadmill absolute claudication walking distance (ACWD) in patients, 40-75 years of age, who have PAD with intermittent claudication in Fontaine stage II and symptom-limited treadmill walking distance.

Secondary objectives include comparing the combination therapy to simvastatin alone for improvement in treadmill pain-free walking distance (PFWD) and ischemic window.

Other secondary objectives include evaluating the safety and tolerability of L-citrulline alone or combined with simvastatin in this patient population and assessing the effects of treatment on quality of life (QOL) as measured by two QOL instruments.

Study Type

Interventional

Enrollment

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Russia
      • Gatchina, Russia, Russian Federation, 188300
        • Municipal Healthcare Institution, Gatchina Central District Hospital
      • Moscow, Russia, Russian Federation, 111539
        • Russian State Medical University at Filatov City Hospital #15
      • Moscow, Russia, Russian Federation, 113811
        • Vishnevsky Institute of Surgery, Russian Medical Academy of Science
      • N. Novgorod, Russia, Russian Federation, 603018
        • Municipal Prophylaxis and Treatment Institution, City Hospital #13
      • Saratov, Russia, Russian Federation, 410056
        • Municipal Medical Institution City Hospital #1 of Saratov
      • St. Petersburg, Russia, Russian Federation, 192242
        • St. Petersburg State Healthcare Institution, Research for Emergency Medical Care
      • St. Petersburg, Russia, Russian Federation, 194354
        • St. Petersburg State Healthcare Institution, Hospital #2
      • St. Petersburg, Russia, Russian Federation, 196247
        • St. Petersburg State Healthcare Institution, Hospital #26
      • St. Petersburg, Russia, Russian Federation, 197089
        • State Educational Institution of Higher Professional Education
      • St. Petersburg, Russia, Russian Federation, 199106
        • St. Petersburg State Healthcare Institution, Pokrovskaya Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

38 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female, 40-75 years of age
  2. If female, post-menopausal for the past year, surgically sterile (i.e., tubal ligation, hysterectomy), or using an adequate method of birth control (i.e., oral contraceptives, double barrier method, IUD cover, sterilized partner, or other method deemed appropriate by Investigator)
  3. If male capable of fathering children, using an adequate method of birth control (i.e., condom or partner using adequate method of birth control)
  4. Peripheral arterial disease with stable, reproducible, intermittent claudication and symptom-limited treadmill walking distance of at least 6 months duration
  5. Rest ankle-brachial index (ABI) ≤0.90 and 10 mm Hg decrease in ankle pressure 1 minute after completing the ETT
  6. ACWD on a standardized (Skinner-Gardner protocol) ETT ≥50 m (164 feet) but ≤300 m (984 feet) determined by the average result on two consecutive ETTs performed at least 7 days apart during the screening phase (Fontaine stage II)
  7. ACWD variability <25% between two consecutive ETTs performed at least 7 days apart during the screening phase. The percent variability is calculated by the difference of the two walking distances divided by the greater of the two walking distances multiplied by 100%. If the variability exceeds 25% a third ETT may be performed and the variability between the second and third test used to determine baseline and inclusion criteria
  8. Willingness to receive dietary counseling and follow a low-cholesterol diet during the study
  9. Ability to give written informed consent and has signed a written informed consent form approved by the Investigator's Independent Ethics Committee (IEC)

Exclusion Criteria:

  1. Critical limb ischemia (defined as presence of rest pain requiring analgesics for more than 2 weeks or the presence of lower limb ulcers or gangrene)
  2. Coronary artery or peripheral artery angioplasty or surgical limb arterial bypass within the last 3 months
  3. Any previous amputation on the lower limbs
  4. Anticipated requirement of surgical or percutaneous revascularization within 3 months of randomization
  5. Currently participating in a supervised exercise regimen
  6. Stroke, myocardial infarction, or deep-vein thrombosis within the last 3 months
  7. Non-atherosclerotic PAD (e.g., thromboangiitis obliterans)
  8. Known abdominal aortic aneurysm ≥4.5 cm
  9. Unstable angina pectoris within the last 3 months
  10. Congestive heart failure (New York Heart Association Class III or IV) despite treatment
  11. Severe, uncontrolled hypertension (sitting systolic blood pressure >180 mm Hg or sitting diastolic blood pressure >95 mm Hg)
  12. Anemia (hemoglobin <10 g/dL in women and 11 g/dL in men) or any clinically significant bleeding episode within the last year
  13. Abnormal platelet count (platelets >150,000/mm3 or <60,000/mm3)
  14. Type I diabetes mellitus or Type II diabetes mellitus if it is accompanied by diabetic peripheral neuropathy
  15. Morbid obesity (body mass index >40 kg/m2)
  16. Severe renal insufficiency (creatinine >221 µmol/L (2.5 mg/dL))
  17. Severe hepatic insufficiency (ALT [SGPT] and AST [SGOT] ≥ 3x upper limit of normal on two separate tests
  18. Any disorder that would affect the interpretation of ETT results
  19. Use of medications that are not allowed and which cannot be discontinued during the study
  20. Participation in an investigational drug or device study within previous 30 days
  21. Underlying disease other than PAD resulting in a life expectancy of less than 1 year
  22. If female, breast feeding, pregnancy confirmed by a positive serum pregnancy test, or using inadequate birth control
  23. Other conditions that could impair informed consent or compliance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Change in absolute claudication walking distance from baseline to end of 12-week double-blind treatment period.

Secondary Outcome Measures

Outcome Measure
Change in pain-free walking distance
Changes in QOL scores from baseline to 12 and 36 weeks
Change in absolute claudication walking distance from baseline to 36 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Chair: William Spickler, MD, PhD, Angiogenix

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Study Registration Dates

First Submitted

July 10, 2006

First Submitted That Met QC Criteria

July 10, 2006

First Posted (Estimate)

July 12, 2006

Study Record Updates

Last Update Posted (Estimate)

October 18, 2006

Last Update Submitted That Met QC Criteria

October 17, 2006

Last Verified

July 1, 2006

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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