Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Evaluation of Cilostazol in Combination With L-Carnitine (ECLECTIC)

This study has been completed.
Sponsor:
Collaborator:
Otsuka Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Colorado Prevention Center
ClinicalTrials.gov Identifier:
NCT00822172
First received: January 13, 2009
Last updated: April 11, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to see how safe and effective L carnitine taken with cilostazol is compared to placebo taken with cilostazol for people with intermittent claudication. A second purpose of the study is to see if L-carnitine is absorbed into the blood stream.


Condition Intervention Phase
Peripheral Vascular Disease
Intermittent Claudication
Peripheral Arterial Disease
Dietary Supplement: Levocarnitine tartrate
Drug: cilostazol
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Evaluation of Cilostazol in Combination With L-Carnitine in Subjects With Intermittent Claudication

Resource links provided by NLM:


Further study details as provided by Colorado Prevention Center:

Primary Outcome Measures:
  • The Effect of Cilostazol Combined With L-carnitine on Change in Peak Walking Time (PWT) Compared to Cilostazol Alone From Baseline/Day 0 to Day 180 in Subjects With Peripheral Artery Disease (PAD) Limited by Intermittent Claudication (IC). [ Time Frame: Day 0 to Day 180 ] [ Designated as safety issue: No ]
  • Safety of Combining Cilostazol With L-carnitine by Evaluating Laboratory Abnormalities and Adverse Events (AEs). [ Time Frame: Day 0 to Day 210 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The Combination of Cilostazol and L-carnitine on PWT Compared to Cilostazol Alone From Baseline/Day 0 to Day 90 in Subjects With Peripheral Artery Disease (PAD) Limited by Intermittent Claudication (IC). [ Time Frame: Day 0 to Day 90 ] [ Designated as safety issue: No ]
  • The Effect of the Combination of Cilostazol and L-carnitine on Claudication Onset Time (COT) and Quality of Life (QOL), as Measured Using the Walking Impairment Questionnaire (WIQ) and SF-36v2® at Days 90 and 180. [ Time Frame: Day 0 to Days 90 and 180 ] [ Designated as safety issue: No ]

Enrollment: 164
Study Start Date: September 2008
Study Completion Date: December 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cilostazol + L-Carnitine Dietary Supplement: Levocarnitine tartrate
Capsule form, 1,002 mg (3 capsules) taken by mouth two times per day (morning and evening). L-carnitine will be taken from Day 0 to Day 180.
Other Names:
  • Carnitine
  • L-carnitine
  • Levocarnitine
Drug: cilostazol

Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.

Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.

Other Name: Pletal
Placebo Comparator: Cilostazol + Placebo Drug: cilostazol

Background therapy beginning at 50mg (1 pill) taken by mouth two times per day for two to three weeks. Then 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for one to two weeks.

Randomized therapy will consist of 100 mg (1 pill) to be taken by mouth two times per day (morning and evening) for approximately 180 days.

Other Name: Pletal

Detailed Description:

Peripheral Artery Disease (PAD) is a narrowing of the blood vessels that supply the leg with blood. It is caused by atherosclerosis (hardening of the arteries).

Muscles require oxygen carried by the blood. When the leg muscles do not get enough blood and oxygen, this can cause pain, cramping, fatigue, and/or discomfort in the leg muscles during walking or exercise. These symptoms are called intermittent claudication (IC). In more severe cases, tissues do not get enough blood and oxygen at rest, and pain may also be present when the legs are resting. Peripheral Artery Disease (PAD)is one of the most common causes of pain and disability in people between 55 and 75 years of age.

Cilostazol is a medication currently available by prescription for intermittent claudication. L-carnitine is an over-the-counter supplement. It is a natural substance in the human body and is also in some red meats, nuts, and energy drinks.

Some subjects in the study will take L-carnitine with cilostazol and others will take placebo with cilostazol. The purpose of this study is to see how safe and effective L carnitine taken with cilostazol is compared to placebo taken with cilostazol for people with intermittent claudication. A placebo is a tablet or pill that looks like regular medication, but it doesn't have any actual medicine in it. A second purpose of the study is to see if L-carnitine is absorbed into the blood stream.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject is >40 years old.
  • The subject has a diagnosis of Intermittent Claudication (IC) due to Peripheral Artery Disease (PAD).
  • Ankle brachial index (ABI) < 0.90 in at least one extremity, or if Ankle brachial index (ABI)is ≥ 0.90 to ≤ 1.0, a reduction of at least 20% in Ankle brachial index (ABI), in at least one extremity, when measured within 1 minute after claudication-limiting treadmill testing. If the subject has non-compressible arteries then a toe brachial index (TBI) < 0.70 is required in at least one extremity.
  • Symptoms of Intermittent Claudication (IC)must be stable for at least 3 months prior to Screening 1.
  • Peak Walking Time (PWT) of ≥ 1 to ≤ 12 minutes on a Gardner protocol at Screening 2.
  • If the subject is currently on statin therapy, they need to have been on statin therapy for at least 3 months prior to Screening 1. Subjects who have recently discontinued statin therapy must "wash-out" for at least one month prior to Screening 1.
  • Tolerance to background therapy of cilostazol (approximately 2 weeks of 50 mg by mouth (PO) twice daily (BID), approximately 1 week of 100 mg PO BID) between Screening 2 and Baseline Visit.
  • Subjects must be either male or females that are post-menopausal, surgically incapable of bearing children or if they are of childbearing potential must have a negative serum pregnancy test at Screening 1 and a negative urine pregnancy test at Day 0 and must agree to use double-barrier contraceptive methods until the end of investigational therapy (Day 180 Visit).
  • The subject is able to comply with scheduled visits, treatment plan and laboratory tests.
  • The subject is willing to participate in this study as documented by written informed consent.
  • During the tolerance phase of the Screening period, the subject demonstrates at least 70% compliance with cilostazol and is willing to continue treatment.

Exclusion Criteria:

  • Evidence of critical limb ischemia (CLI) (e.g., ischemic rest pain or ischemic ulceration).
  • The subject has had a major amputation of the leg or any other amputation that limits walking ability.
  • The subject has diabetes mellitus type 1 or poorly controlled diabetes mellitus type 2 (hemoglobin A1c (HbA1c) > 10).
  • The subject has had a transient ischemic attack (TIA) or deep vein thrombosis in the last 3 months.
  • The subject has had a stroke within the last 6 months.
  • The subject has participated in an angiogenic gene therapy study, unless known to be given placebo.
  • The subject has any of the following laboratory parameters at Screening 1:

    • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin >3 times the upper limit of normal (ULN)
    • Serum creatinine >2.5 mg/dL
    • Hemoglobin (Hb) <10 g/dL
    • White blood cell (WBC) count <3.0 x 103/µL; or > 15 x 103/µL
    • Platelet count <100 x 103/µL
  • The subject walks less than 1 minute at 2 miles per hour (mph), 0% grade as determined during the Screening 1 treadmill familiarization.
  • The subject has clinically significant electrocardiogram (ECG) abnormalities at rest or changes during exercise or post-exercise at Screening 2 or Day 0.
  • The subject has any history or clinical evidence of congestive heart failure (CHF), with which the clinician-investigator concurs.
  • The subject has uncontrolled hypertension (resting blood pressure (BP) > 180/100 mmHg) or uncontrolled arrhythmic disorders at Screening 1.
  • History of coronary or peripheral revascularization within 6 months prior to Screening 1.
  • The subject plans to undergo coronary or peripheral revascularization during the course of the study.
  • The subject is currently taking L-carnitine or medication for claudication (including pentoxifylline or cilostazol). In this situation, the subject would become eligible for Screening 1 after a 6 week washout of the medication.
  • Subjects currently taking or those who anticipate taking ketoconazole, itraconazole, or erythromycin. The subject would become eligible for Screening 1 immediately after completion of therapy or discontinuation of the drug(s).
  • The subject has a known, active malignancy that requires active anti-neoplastic therapy. (stable basal cell skin cancer allowed. Cancer being treated soley with hormonal therapy is allowed.)
  • The subject has a severe co-morbidity with an expected survival of less than 2 years.
  • The subject's Peak Walking Time (PWT) is limited by symptoms other than claudication (e.g., shortness of breath (SOB), fatigue, angina, arthritis, etc.). If, in the opinion of the investigator, the subject were to improve their Peak Walking Time (PWT) from study therapy to the extent that his or her walking would then be limited by a symptom other than claudication, the subject should not be enrolled.
  • The subject has a history of alcohol or other substance abuse within 6 months of Screening 1.
  • The subject has an inability to tolerate oral medication administration.
  • The subject has a known or suspected allergy to the study medication(s) or class of study medication(s) (cilostazol or L-carnitine) to be administered.
  • The subject has initiated an exercise training program within 3 months of Screening 1, has the inability to maintain his or her current level of physical activity throughout the study, or the subject plans on enrolling in an exercise training program during the study.
  • The subject plans to change his/her smoking status during the planned duration of this study (subjects will be advised that stopping smoking is best for his/her health).
  • The subject is currently pregnant or breastfeeding.
  • The subject has received an investigational drug or biological agent within 30 days prior to Screening 1.
  • The subject is currently participating in or plans to enroll in another clinical trial during this study.
  • The subject has any other clinically significant medical or psychiatric condition that in the opinion of the Investigator could impact the subject's ability to successfully complete this trial.
  • In the Investigator's opinion, the subject experienced any Adverse Events (AEs) during the tolerance phase of the Screening period that present a potential ongoing safety concern.
  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: NCT00822172

  Show 24 Study Locations
Sponsors and Collaborators
Colorado Prevention Center
Otsuka Pharmaceutical Co., Ltd.
Investigators
Study Chair: Neil Goldenberg, MD, PhD University of Colorado Heather Sciences Center
  More Information

Additional Information:
Publications:
Hiatt WR. Management of Intermittent Claudication. Contemporary Diagnosis and management of Peripheral arterial Disease. 1 ed. Newtown: Handvbooks in Healthcare Co., Inc., 2004:51-9
Rizza v, Lorefice R, Rizza N et al. Pharmacokinetics of L-Carnitine in Human Subjects. In: Ferrari R, DiMauro S, Sherwood G, eds. L-Carnitine and its Role in Medicine: From Function to Therapy. 1 ed San Diego: Academic Press, Inc., 1992:63-77.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Colorado Prevention Center
ClinicalTrials.gov Identifier: NCT00822172     History of Changes
Other Study ID Numbers: CPC-08-01
Study First Received: January 13, 2009
Results First Received: March 1, 2013
Last Updated: April 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Colorado Prevention Center:
Peripheral Vascular Disease
Peripheral Arterial Disease
Intermittent Claudication
Peak Walking Time
Claudication Onset Time
Cilostazol
Carnitine

Additional relevant MeSH terms:
Intermittent Claudication
Peripheral Arterial Disease
Peripheral Vascular Diseases
Vascular Diseases
Arterial Occlusive Diseases
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Signs and Symptoms
Carnitine
Cilostazol
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Central Nervous System Agents
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Growth Substances
Hematologic Agents
Micronutrients
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on November 25, 2014