ECLECTIC: Evaluation of Cilostazol in Combination With L-Carnitine

Sponsor
Colorado Prevention Center (Other)
Overall Status
Completed
CT.gov ID
NCT00822172
Collaborator
Otsuka Pharmaceutical Co., Ltd. (Industry)
164
24
2
27
6.8
0.3

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
164 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
Evaluation of Cilostazol in Combination With L-Carnitine in Subjects With Intermittent Claudication
Study Start Date :
Sep 1, 2008
Actual Primary Completion Date :
Nov 1, 2010
Actual Study Completion Date :
Dec 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Cilostazol + L-Carnitine

1 tablet cilostazol 100 mg PO BID and 3 capsules L-carnitine 334 mg PO BID

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 Names:
  • Pletal
  • Placebo Comparator: Cilostazol + Placebo

    1 tablet cilostazol 100 mg PO BID and 3 capsules placebo PO BID

    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 Names:
  • Pletal
  • Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Peak Walking Time (PWT) at Day 180 [Baseline, Day 180]

      Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. This maximum time walked is referred to as the peak walking time (PWT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.

    Secondary Outcome Measures

    1. Change From Baseline in Peak Walking Time at Day 180 [Baseline, Day 180]

      Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. This maximum time walked is referred to as the peak walking time (PWT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.

    2. Change From Baseline in Peak Walking Time at Day 90 [Baseline, Day 90]

      Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. This maximum time walked is referred to as the peak walking time (PWT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.

    3. Change From Baseline in Claudication Onset Time at Day 180 [Baseline, Day 180]

      Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. The time during the conduct of the exercise treadmill test at which the subject first reported claudication symptoms is referred to as the claudication onset time (COT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.

    4. Change From Baseline in Claudication Onset Time at Day 90 [Baseline, Day 90]

      Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. The time during the conduct of the exercise treadmill test at which the subject first reported claudication symptoms is referred to as the claudication onset time (COT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.

    5. Change From Baseline in Walking Impairment Questionnaire for Walking Distance at Day 180 [Baseline, Day 180]

      Subjects completed the Walking Impairment Questionnaire (WIQ) whereby they were asked about their maximal walking distance before having to rest as a result of claudication symptoms associated with their peripheral artery disease (PAD). The WIQ was administered at the Baseline, Day 90, and Day 180 visits. On the WIQ subjects were asked a series of questions related to their degree of physical difficulty that best described how hard it was for the subject to walk on level ground without stopping to rest. The questions began by asking the degree of difficulty walking around indoors, then 50 feet, 150 feet, 300 feet, 600 feet, 900 feet, and lastly 1500 feet. The responses range from None (best outcome) to Slight, then Some, then Much, then lastly Unable (worst outcome). The walking distance score was calculated from the 7 questions in the section by way of a weighted sum. A score of 100 indicated no walking impairment. A score of 0 corresponded to the highest degree of walking impairment

    6. Change From Baseline in Walking Impairment Questionnaire for Walking Distance at Day 90 [Baseline, Day 90]

      Subjects completed the Walking Impairment Questionnaire (WIQ) whereby they were asked about their maximal walking distance before having to rest as a result of claudication symptoms associated with their peripheral artery disease (PAD). The WIQ was administered at the Baseline, Day 90, and Day 180 visits. On the WIQ subjects were asked a series of questions related to their degree of physical difficulty that best described how hard it was for the subject to walk on level ground without stopping to rest. The questions began by asking the degree of difficulty walking around indoors, then 50 feet, 150 feet, 300 feet, 600 feet, 900 feet, and lastly 1500 feet. The responses range from None (best outcome) to Slight, then Some, then Much, then lastly Unable (worst outcome). The walking distance score was calculated from the 7 questions in the section by way of a weighted sum. A score of 100 indicated no walking impairment. A score of 0 corresponded to the highest degree of walking impairment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    • 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

    • 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

    Locations

    Site City State Country Postal Code
    1 Internal Medicine Physicians Associates Phoenix Arizona United States 85006
    2 Tatum Ridge Internal Medicine Phoenix Arizona United States 85032
    3 Central Arkansas Veteran's Healthcare System Little Rock Arkansas United States 72205
    4 VA Palo Alto Health Care System Palo Alto California United States 94304
    5 University of California at Davis Vascular Center Sacramento California United States 95817
    6 Sacramento Heart and Vascular Research Center Sacramento California United States 95825
    7 Apex Research Institute Santa Ana California United States 92705
    8 Aurora Denver Cardiology Associates Aurora Colorado United States 80012
    9 Aurora Denver Cardiology Associates Denver Colorado United States 80218
    10 Pensacola Research Consultants, Inc. Pensacola Florida United States 32504
    11 DMI Healthcare Group, Inc. Pinellas Park Florida United States 33782
    12 Meridian Research Saint Petersburg Florida United States 33709
    13 Ochsner Medical Center New Orleans Louisiana United States 70121
    14 HPV Heart, PA Columbia Maryland United States 21044
    15 University of Massachusetts Medical Center Worcester Massachusetts United States 01605
    16 Dartmouth-Hitchcock Medical Center Lebanon New Hampshire United States 03756
    17 University of Rochester Medical Center Rochester New York United States 14623
    18 Durham VA-Medical Center Durham North Carolina United States 27705
    19 Radiant Research, Inc Columbus Ohio United States 43212
    20 Jobst Vascular Center Toledo Ohio United States 43606
    21 Peripheral Vascular Associates San Antonio Texas United States 78205
    22 Clinical Trials of Texas, Inc. San Antonio Texas United States 78229
    23 Radiant Research- Salt Lake City Salt Lake City Utah United States 84107
    24 Beloit Clinic Research Office Beloit Wisconsin United States 53511

    Sponsors and Collaborators

    • Colorado Prevention Center
    • Otsuka Pharmaceutical Co., Ltd.

    Investigators

    • Study Chair: Neil Goldenberg, MD, PhD, University of Colorado Heather Sciences Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Colorado Prevention Center
    ClinicalTrials.gov Identifier:
    NCT00822172
    Other Study ID Numbers:
    • CPC-08-01
    First Posted:
    Jan 14, 2009
    Last Update Posted:
    Nov 29, 2019
    Last Verified:
    Nov 1, 2019

    Study Results

    Participant Flow

    Recruitment Details The first participant was randomized on September 19th, 2008 and the last subject was randomized on May 7, 2010. Clinical study sites were a mixture of university/hospital settings, Veteran Affairs hospitals, professional research centers and medical clinics.
    Pre-assignment Detail The study included a cilostazol run in period. From the 164 participants who remained eligible at the end of the run in period, only 1 participant did not subsequently receive treatment. This was due to voluntary withdrawal by the participant.
    Arm/Group Title Cilostazol + L-Carnitine Cilostazol + Placebo
    Arm/Group Description 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. 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. 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.
    Period Title: Overall Study
    STARTED 80 83
    COMPLETED 65 64
    NOT COMPLETED 15 19

    Baseline Characteristics

    Arm/Group Title Cilostazol + L-Carnitine Cilostazol + Placebo Total
    Arm/Group Description 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. 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. 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. Total of all reporting groups
    Overall Participants 80 83 163
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    43
    53.8%
    27
    32.5%
    70
    42.9%
    >=65 years
    37
    46.3%
    56
    67.5%
    93
    57.1%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.8
    (9.39)
    67.3
    (8.00)
    66.5
    (8.74)
    Sex: Female, Male (Count of Participants)
    Female
    14
    17.5%
    16
    19.3%
    30
    18.4%
    Male
    66
    82.5%
    67
    80.7%
    133
    81.6%
    Region of Enrollment (participants) [Number]
    United States
    80
    100%
    83
    100%
    163
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in Peak Walking Time (PWT) at Day 180
    Description Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. This maximum time walked is referred to as the peak walking time (PWT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
    Time Frame Baseline, Day 180

    Outcome Measure Data

    Analysis Population Description
    modified Intent to Treat Population (mITT)
    Arm/Group Title Cilostazol + L-Carnitine Cilostazol + Placebo
    Arm/Group Description 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. 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. 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.
    Measure Participants 74 71
    Mean (Standard Deviation) [Log Minutes]
    0.241
    (0.3836)
    0.134
    (0.3343)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cilostazol + L-Carnitine, Cilostazol + Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.076
    Comments
    Method two-sample equal-variances t-test
    Comments
    2. Secondary Outcome
    Title Change From Baseline in Peak Walking Time at Day 180
    Description Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. This maximum time walked is referred to as the peak walking time (PWT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
    Time Frame Baseline, Day 180

    Outcome Measure Data

    Analysis Population Description
    Per Protocol (PP) Population
    Arm/Group Title Cilostazol + L-Carnitine Cilostazol + Placebo
    Arm/Group Description 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. 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. 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.
    Measure Participants 60 58
    Mean (Standard Deviation) [Log Minutes]
    0.267
    (0.3516)
    0.145
    (0.3124)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cilostazol + L-Carnitine, Cilostazol + Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.048
    Comments
    Method two-sample equal-variances t-test
    Comments
    3. Secondary Outcome
    Title Change From Baseline in Peak Walking Time at Day 90
    Description Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. This maximum time walked is referred to as the peak walking time (PWT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
    Time Frame Baseline, Day 90

    Outcome Measure Data

    Analysis Population Description
    modified Intent to Treat Population (mITT)
    Arm/Group Title Cilostazol + L-Carnitine Cilostazol + Placebo
    Arm/Group Description 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. 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. 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.
    Measure Participants 69 65
    Mean (Standard Deviation) [Log Minutes]
    0.166
    (0.3571)
    0.139
    (0.3293)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cilostazol + L-Carnitine, Cilostazol + Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.650
    Comments
    Method two-sample equal-variances t-test
    Comments
    4. Secondary Outcome
    Title Change From Baseline in Claudication Onset Time at Day 180
    Description Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. The time during the conduct of the exercise treadmill test at which the subject first reported claudication symptoms is referred to as the claudication onset time (COT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
    Time Frame Baseline, Day 180

    Outcome Measure Data

    Analysis Population Description
    modified Intent to Treat Population (mITT)
    Arm/Group Title Cilostazol + L-Carnitine Cilostazol + Placebo
    Arm/Group Description 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. 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. 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.
    Measure Participants 66 66
    Mean (Standard Deviation) [Log Minutes]
    1.065
    (0.6680)
    0.896
    (0.7364)
    5. Secondary Outcome
    Title Change From Baseline in Claudication Onset Time at Day 90
    Description Subjects were asked to complete a standardized exercise treadmill test using a modified Gardner protocol. Subjects walked on the treadmill until they were physically unable to walk further either as a result of their peripheral artery disease (PAD) symptoms or other non-PAD symptoms. The time during the conduct of the exercise treadmill test at which the subject first reported claudication symptoms is referred to as the claudication onset time (COT) and reported in minutes/seconds. The exercise treadmill test was conducted at Screening, Baseline, Day 90, and Day 180 visits. The log transformation is used to make highly skewed distributions less skewed.
    Time Frame Baseline, Day 90

    Outcome Measure Data

    Analysis Population Description
    modified Intent to Treat Population (mITT)
    Arm/Group Title Cilostazol + L-Carnitine Cilostazol + Placebo
    Arm/Group Description 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. 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. 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.
    Measure Participants 68 63
    Mean (Standard Deviation) [Log Minutes]
    1.001
    (0.6476)
    0.815
    (0.7000)
    6. Secondary Outcome
    Title Change From Baseline in Walking Impairment Questionnaire for Walking Distance at Day 180
    Description Subjects completed the Walking Impairment Questionnaire (WIQ) whereby they were asked about their maximal walking distance before having to rest as a result of claudication symptoms associated with their peripheral artery disease (PAD). The WIQ was administered at the Baseline, Day 90, and Day 180 visits. On the WIQ subjects were asked a series of questions related to their degree of physical difficulty that best described how hard it was for the subject to walk on level ground without stopping to rest. The questions began by asking the degree of difficulty walking around indoors, then 50 feet, 150 feet, 300 feet, 600 feet, 900 feet, and lastly 1500 feet. The responses range from None (best outcome) to Slight, then Some, then Much, then lastly Unable (worst outcome). The walking distance score was calculated from the 7 questions in the section by way of a weighted sum. A score of 100 indicated no walking impairment. A score of 0 corresponded to the highest degree of walking impairment
    Time Frame Baseline, Day 180

    Outcome Measure Data

    Analysis Population Description
    modified Intent to Treat Population (mITT)
    Arm/Group Title Cilostazol + L-Carnitine Cilostazol + Placebo
    Arm/Group Description 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. 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. 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.
    Measure Participants 68 68
    Mean (Standard Deviation) [score on a scale]
    13.20
    (22.001)
    6.57
    (24.288)
    7. Secondary Outcome
    Title Change From Baseline in Walking Impairment Questionnaire for Walking Distance at Day 90
    Description Subjects completed the Walking Impairment Questionnaire (WIQ) whereby they were asked about their maximal walking distance before having to rest as a result of claudication symptoms associated with their peripheral artery disease (PAD). The WIQ was administered at the Baseline, Day 90, and Day 180 visits. On the WIQ subjects were asked a series of questions related to their degree of physical difficulty that best described how hard it was for the subject to walk on level ground without stopping to rest. The questions began by asking the degree of difficulty walking around indoors, then 50 feet, 150 feet, 300 feet, 600 feet, 900 feet, and lastly 1500 feet. The responses range from None (best outcome) to Slight, then Some, then Much, then lastly Unable (worst outcome). The walking distance score was calculated from the 7 questions in the section by way of a weighted sum. A score of 100 indicated no walking impairment. A score of 0 corresponded to the highest degree of walking impairment
    Time Frame Baseline, Day 90

    Outcome Measure Data

    Analysis Population Description
    modified Intent to Treat Population (mITT)
    Arm/Group Title Cilostazol + L-Carnitine Cilostazol + Placebo
    Arm/Group Description 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. 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. 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.
    Measure Participants 71 66
    Mean (Standard Deviation) [score on a scale]
    12.98
    (25.251)
    10.01
    (21.354)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Cilostazol + L-Carnitine Cilostazol + Placebo
    Arm/Group Description 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. 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. 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.
    All Cause Mortality
    Cilostazol + L-Carnitine Cilostazol + Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Cilostazol + L-Carnitine Cilostazol + Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/80 (13.8%) 10/83 (12%)
    Cardiac disorders
    Coronary artery disease 1/80 (1.3%) 1 1/83 (1.2%) 1
    Supraventricular tachycardia 0/80 (0%) 0 1/83 (1.2%) 1
    Angina pectoris 0/80 (0%) 0 1/83 (1.2%) 1
    Atrial fibrillation 0/80 (0%) 0 1/83 (1.2%) 1
    Myocardial infarction 2/80 (2.5%) 3 0/83 (0%) 0
    Sick sinus syndrome 1/80 (1.3%) 1 0/83 (0%) 0
    Endocrine disorders
    Pancreatitis acute 1/80 (1.3%) 1 0/83 (0%) 0
    Gastrointestinal disorders
    Colitis 0/80 (0%) 0 1/83 (1.2%) 1
    General disorders
    Abdominal hernia 2/80 (2.5%) 2 0/83 (0%) 0
    Musculoskeletal and connective tissue disorders
    Cervicobrachial syndrome 1/80 (1.3%) 1 0/83 (0%) 0
    Cellulitis 1/80 (1.3%) 1 0/83 (0%) 0
    Back pain 1/80 (1.3%) 1 0/83 (0%) 0
    Renal and urinary disorders
    Prostate cancer 0/80 (0%) 0 1/83 (1.2%) 1
    Urosepsis 0/80 (0%) 0 1/83 (1.2%) 1
    Ureteric fistula 1/80 (1.3%) 1 0/83 (0%) 0
    Vascular disorders
    Arterial thrombosis limb 0/80 (0%) 0 1/83 (1.2%) 1
    Cerebrovascular accident 0/80 (0%) 0 1/83 (1.2%) 1
    Peripheral arterial occlusive disease 0/80 (0%) 0 1/83 (1.2%) 1
    Other (Not Including Serious) Adverse Events
    Cilostazol + L-Carnitine Cilostazol + Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/80 (23.8%) 22/83 (26.5%)
    Gastrointestinal disorders
    Diarrhoea 9/80 (11.3%) 16 8/83 (9.6%) 17
    Nervous system disorders
    Headache 10/80 (12.5%) 15 14/83 (16.9%) 17

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title William Hiatt, MD, President
    Organization CPC Clinical Research
    Phone 3038609900
    Email william.hiatt@cpcmed.org
    Responsible Party:
    Colorado Prevention Center
    ClinicalTrials.gov Identifier:
    NCT00822172
    Other Study ID Numbers:
    • CPC-08-01
    First Posted:
    Jan 14, 2009
    Last Update Posted:
    Nov 29, 2019
    Last Verified:
    Nov 1, 2019