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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2006 by Angiogenix.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Angiogenix
ClinicalTrials.gov Identifier:
NCT00351286
First received: July 10, 2006
Last updated: October 17, 2006
Last verified: July 2006
  Purpose

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.


Condition Intervention Phase
Peripheral Arterial Disease
Intermittent Claudication
Drug: L-citrulline tablets, 1000 mg
Drug: Placebo tablets matching L-citrulline tablets
Drug: Background simvastatin at a stable dose of 40 mg qHS
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Angiogenix:

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

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 160
Study Start Date: March 2006
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.

  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00351286

Locations
Russian Federation
Municipal Healthcare Institution, Gatchina Central District Hospital
Gatchina, Russia, Russian Federation, 188300
Russian State Medical University at Filatov City Hospital #15
Moscow, Russia, Russian Federation, 111539
Vishnevsky Institute of Surgery, Russian Medical Academy of Science
Moscow, Russia, Russian Federation, 113811
Municipal Prophylaxis and Treatment Institution, City Hospital #13
N. Novgorod, Russia, Russian Federation, 603018
Municipal Medical Institution City Hospital #1 of Saratov
Saratov, Russia, Russian Federation, 410056
St. Petersburg State Healthcare Institution, Research for Emergency Medical Care
St. Petersburg, Russia, Russian Federation, 192242
St. Petersburg State Healthcare Institution, Hospital #2
St. Petersburg, Russia, Russian Federation, 194354
State Educational Institution of Higher Professional Education
St. Petersburg, Russia, Russian Federation, 197089
St. Petersburg State Healthcare Institution, Pokrovskaya Hospital
St. Petersburg, Russia, Russian Federation, 199106
St. Petersburg State Healthcare Institution, Hospital #26
St. Petersburg, Russia, Russian Federation, 196247
Sponsors and Collaborators
Angiogenix
Investigators
Study Chair: William Spickler, MD, PhD Angiogenix
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00351286     History of Changes
Other Study ID Numbers: ANGX-1039-02
Study First Received: July 10, 2006
Last Updated: October 17, 2006
Health Authority: Russia: Ministry of Health of the Russian Federation

Keywords provided by Angiogenix:
peripheral arterial disease
peripheral vascular disease
claudication

Additional relevant MeSH terms:
Intermittent Claudication
Peripheral Arterial Disease
Peripheral Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Signs and Symptoms
Atherosclerosis
Simvastatin
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014