Trial Outcomes & Findings for Effect of Vitamin D Supplementation on Exercise Adaptations in Patients on Statin Therapy (NCT NCT02030041)

NCT ID: NCT02030041

Last Updated: 2017-03-31

Results Overview

Peak oxygen consumption( VO2peak) is defined as the highest rate at which oxygen can be taken up and utilized by the body during severe exercise. The participants were encouraged to exercise to exhaustion with progressive 2-minutes increments in the power output during the test. VO2peak was obtained when participants reached volitional exhaustion and met at least one of the following criteria: plateau in oxygen consumption despite increase in workload, rating of perceived exertion \>18, Respiratory exchange ratio \> 1.10 and peak heart rate within 10 beats of age predicted maximum. . As VO2peak (expressed as liters of oxygen consumed per minute) is also dependent on age, sex, and body size, it was expressed as percentage of the predicted value(VO2peak%).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 33 participants
• Primary outcome timeframe: Twelve weeks
• Results posted on: 2017-03-31

Participant Flow

Participant milestones

Measure	Simvastatin and Placebo Eleven participants will be vitamin D deficient with LDL-C between 100 to 130mg/dl This arm will receive simvastatin 40 mg once daily and placebo once weekly , and will exercise for twelve weeks	Simvastatin and Vitamin D Eleven participants will be vitamin D deficient with LDL-C between 100 to 130mg/dl This arm will receive Simvastatin 40 mg once daily and vitamin D 60000 units once weekly, and will exercise for twelve weeks	Vitamin D and Placebo Eleven participants will be vitamin D deficient with LDL-C between 100 to 130mg/dl This arm will receive vitamin D 60,000 units once weekly and placebo once daily, and will exercise for twelve weeks
Overall Study STARTED	11	11	11
Overall Study COMPLETED	9	9	10
Overall Study NOT COMPLETED	2	2	1

Reasons for withdrawal

Measure	Simvastatin and Placebo Eleven participants will be vitamin D deficient with LDL-C between 100 to 130mg/dl This arm will receive simvastatin 40 mg once daily and placebo once weekly , and will exercise for twelve weeks	Simvastatin and Vitamin D Eleven participants will be vitamin D deficient with LDL-C between 100 to 130mg/dl This arm will receive Simvastatin 40 mg once daily and vitamin D 60000 units once weekly, and will exercise for twelve weeks	Vitamin D and Placebo Eleven participants will be vitamin D deficient with LDL-C between 100 to 130mg/dl This arm will receive vitamin D 60,000 units once weekly and placebo once daily, and will exercise for twelve weeks
Overall Study Withdrawal by Subject	2	2	1

Baseline Characteristics

Effect of Vitamin D Supplementation on Exercise Adaptations in Patients on Statin Therapy

Baseline characteristics by cohort

Measure	Simvastatin and Placebo n=9 Participants Participants took simvastatin 40 mg once daily and performed exercise for 12 weeks	Simvastatin and Vitamin D n=9 Participants Participants took simvastatin 40 mg once daily and vitamin D 60,000 units once weekly, and performed exercise for 12 weeks	Vitamin D and Placebo n=10 Participants Participants took vitamin D 60000 units once weekly and performed exercise for 12 weeks	Total n=28 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	9 Participants n=7 Participants	10 Participants n=5 Participants	28 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants	23 Participants n=4 Participants
Race/Ethnicity, Customized Asian Indian	9 participants n=5 Participants	9 participants n=7 Participants	10 participants n=5 Participants	28 participants n=4 Participants
Region of Enrollment India	9 participants n=5 Participants	9 participants n=7 Participants	10 participants n=5 Participants	28 participants n=4 Participants
Body mass index(BMI)	27.9 kg/m2 STANDARD_DEVIATION 2.4 • n=5 Participants	28.1 kg/m2 STANDARD_DEVIATION 2.5 • n=7 Participants	27.4 kg/m2 STANDARD_DEVIATION 2.2 • n=5 Participants	27.8 kg/m2 STANDARD_DEVIATION 2.4 • n=4 Participants
HbA1c	6.9 % STANDARD_DEVIATION 0.4 • n=5 Participants	6.9 % STANDARD_DEVIATION 0.5 • n=7 Participants	6.9 % STANDARD_DEVIATION 0.5 • n=5 Participants	6.9 % STANDARD_DEVIATION 0.5 • n=4 Participants
Fasting plasma Insulin	13.6 microIU/ml STANDARD_DEVIATION 6.3 • n=5 Participants	12.1 microIU/ml STANDARD_DEVIATION 5 • n=7 Participants	13.2 microIU/ml STANDARD_DEVIATION 4.5 • n=5 Participants	13.1 microIU/ml STANDARD_DEVIATION 5.2 • n=4 Participants
Low density Cholesterol (LDL-C)	117.4 mg/dl STANDARD_DEVIATION 9.4 • n=5 Participants	116.4 mg/dl STANDARD_DEVIATION 11.4 • n=7 Participants	112 mg/dl STANDARD_DEVIATION 6.8 • n=5 Participants	115.2 mg/dl STANDARD_DEVIATION 9.3 • n=4 Participants
Peak oxygen consumption(VO2peak)	1.33 L/min STANDARD_DEVIATION 0.5 • n=5 Participants	1.13 L/min STANDARD_DEVIATION 0.4 • n=7 Participants	1.1 L/min STANDARD_DEVIATION 0.2 • n=5 Participants	1.2 L/min STANDARD_DEVIATION 0.4 • n=4 Participants
Peak oxygen consumption percentage of predicted value (VO2peak%)	52.2 % STANDARD_DEVIATION 9.8 • n=5 Participants	52.2 % STANDARD_DEVIATION 8.9 • n=7 Participants	46.4 % STANDARD_DEVIATION 8.6 • n=5 Participants	50.1 % STANDARD_DEVIATION 9.2 • n=4 Participants
Skeletal muscle citrate synthase activity	0.0051 change in mOD/min at 412nm STANDARD_DEVIATION 0.0001 • n=5 Participants	0.0042 change in mOD/min at 412nm STANDARD_DEVIATION 0.0019 • n=7 Participants	0.0043 change in mOD/min at 412nm STANDARD_DEVIATION 0.0017 • n=5 Participants	0.0046 change in mOD/min at 412nm STANDARD_DEVIATION 0.0013 • n=4 Participants

PRIMARY outcome

Timeframe: Twelve weeks

Peak oxygen consumption( VO2peak) is defined as the highest rate at which oxygen can be taken up and utilized by the body during severe exercise. The participants were encouraged to exercise to exhaustion with progressive 2-minutes increments in the power output during the test. VO2peak was obtained when participants reached volitional exhaustion and met at least one of the following criteria: plateau in oxygen consumption despite increase in workload, rating of perceived exertion >18, Respiratory exchange ratio > 1.10 and peak heart rate within 10 beats of age predicted maximum. . As VO2peak (expressed as liters of oxygen consumed per minute) is also dependent on age, sex, and body size, it was expressed as percentage of the predicted value(VO2peak%).

Outcome measures

Measure	Simvastatin and Placebo n=9 Participants Participants received simvastatin 40 mg once daily and performed exercise for 12 weeks	Simvastatin and Vitamin D n=9 Participants Participants received simvastatin 40 mg once daily and vitamin D 60,000 units once weekly, and performed exercise for 12 weeks	Vitamin D and Placebo n=10 Participants Participants received vitamin D 60,000 units once weekly and performed exercise for 12 weeks
Peak Oxygen Consumption	43.8 percentage of predicted value Standard Deviation 7.3	51.6 percentage of predicted value Standard Deviation 10.5	53.5 percentage of predicted value Standard Deviation 10.4

PRIMARY outcome

Timeframe: Twelve weeks

Skeletal muscle citrate synthase activity is a validated marker of mitochondrial content. Skeletal muscle biopsy was obtained from vastus lateralis muscle of five patients in either groups before and after the intervention. Under aseptic conditions, samples were taken in protease inhibitor cocktail and stored at -80ºC. Mitochondrial citrate synthase activity (the working range of the kit was 1.56-100 µg/mL, with intra and inter assay CV of 4.35-6.55 % and 8.3 % respectively) was measured using ELISA Kit (Abcam, Cambridge, UK) as per manufacturer's instructions.Skeletal muscle citrate synthase activity is a validated marker of mitochondrial content.

Outcome measures

Measure	Simvastatin and Placebo n=9 Participants Participants received simvastatin 40 mg once daily and performed exercise for 12 weeks	Simvastatin and Vitamin D n=9 Participants Participants received simvastatin 40 mg once daily and vitamin D 60,000 units once weekly, and performed exercise for 12 weeks	Vitamin D and Placebo n=10 Participants Participants received vitamin D 60,000 units once weekly and performed exercise for 12 weeks
Skeletal Muscle Mitochondrial Content	0.005 change in mOD/min at 412nm Standard Deviation 0.0007	0.005 change in mOD/min at 412nm Standard Deviation 0.0001	0.0052 change in mOD/min at 412nm Standard Deviation 0.0001

Adverse Events

Simvastatin and Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Simvastatin and Vitamin D

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Vitamin D and Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Simvastatin and Placebo n=9 participants at risk Eleven participants will be vitaminD deficient with LDL-C between 100 to 130mg/dl This arm will receive Simvastatin 40 mg once daily and placebo once weekly, and will exercise for twelve weeks Simvastatin: Simvastatin in a dose of 40 mg will be provided to the study participants Placebo: Placebo will be provided to the study participants	Simvastatin and Vitamin D n=9 participants at risk Eleven participants will be vitamin D deficient with LDL-C between 100 to 130mg/dl This arm will receive simvastatin 40 mg once daily and vitamin D 60,000 units once weekly , and will exercise for twelve weeks Vitamin D: Vitamin D will be given to achieve normal serum levels Simvastatin: Simvastatin in a dose of 40 mg will be provided to the study participants	Vitamin D and Placebo n=10 participants at risk Eleven participants will be vitamin D deficient with LDL-C between 100 to 130mg/dl This arm will receive vitamin D 60,000 units once weekly and placebo once daily, and will exercise for twelve weeks Vitamin D: Vitamin D will be given to achieve normal serum levels Placebo: Placebo will be provided to the study participants
Musculoskeletal and connective tissue disorders Myalgia	22.2% 2/9	11.1% 1/9	0.00% 0/10

Additional Information

Anil Bhansali

PGIMER

Phone: 01722756583

Email: ashuendo@gmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place