Study: NCT02947750

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: 6R-BH4
Description: Participants will receive 200 mg of 6R-BH4 twice daily for 12 weeks. Study pills are dissolved in water or apple juice, and taken with food.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: 6R-BH4
Description: Participants will receive 200 mg of 6R-BH4 twice daily for 12 weeks. Study pills are dissolved in water or apple juice, and taken with food.

Intervention type: OTHER
Group type: ACTIVE_COMPARATOR
Intervention: 6R-BH4 placebo
Description: Participants will receive a placebo that is identical to 200 mg of 6R-BH4. The placebo will be taken twice daily for 12 weeks. Study pills are dissolved in water or apple juice, and taken with food.

Intervention type: OTHER
Group type: PLACEBO_COMPARATOR
Intervention: 6R-BH4 placebo
Description: Participants will receive a placebo that is identical to 200 mg of 6R-BH4. The placebo will be taken twice daily for 12 weeks. Study pills are dissolved in water or apple juice, and taken with food.

Intervention type: DIETARY_SUPPLEMENT
Group type: EXPERIMENTAL
Intervention: Folic acid
Description: Participants will take 1 mg of folic acid daily for 12 weeks. Folic acid is given because it enhances the binding affinity of BH4 to nitric oxide synthase (NOS), and also enhances the regeneration of BH4 from inactive BH2

Intervention type: DIETARY_SUPPLEMENT
Group type: ACTIVE_COMPARATOR
Intervention: Folic acid
Description: Participants will take 1 mg of folic acid daily for 12 weeks. Folic acid is given because it enhances the binding affinity of BH4 to nitric oxide synthase (NOS), and also enhances the regeneration of BH4 from inactive BH2

Intervention type: DIETARY_SUPPLEMENT
Group type: ACTIVE_COMPARATOR
Intervention: Folic acid
Description: Participants will take 1 mg of folic acid daily for 12 weeks. Folic acid is given because it enhances the binding affinity of BH4 to nitric oxide synthase (NOS), and also enhances the regeneration of BH4 from inactive BH2

Intervention type: DIETARY_SUPPLEMENT
Group type: PLACEBO_COMPARATOR
Intervention: Folic acid
Description: Participants will take 1 mg of folic acid daily for 12 weeks. Folic acid is given because it enhances the binding affinity of BH4 to nitric oxide synthase (NOS), and also enhances the regeneration of BH4 from inactive BH2

Intervention type: OTHER
Group type: EXPERIMENTAL
Intervention: Exercise training
Description: Participants will exercise 3 times a week on a stationary ergometer. Exercise intensity will begin at low levels (50% of maximal heart rate reserve) calculated utilizing the Karvonen method. Briefly, target exercise heart rate (HR) is calculated by subtracting the persons age from 220. Resting heart rate is then subtracted from this number. The answer is then multiplied by the target percent (50% for example) and the product is added back to resting heart rate to provide the target exercise session heart rate. Intensity will be increased by 5% every week (as tolerated by the participant) to a maximum of 80% of maximal heart rate. Exercise time will progress from an initial 20 minutes per session to a maximum of 45 minutes by increasing 5 minutes each week.

Intervention type: OTHER
Group type: ACTIVE_COMPARATOR
Intervention: Exercise training
Description: Participants will exercise 3 times a week on a stationary ergometer. Exercise intensity will begin at low levels (50% of maximal heart rate reserve) calculated utilizing the Karvonen method. Briefly, target exercise heart rate (HR) is calculated by subtracting the persons age from 220. Resting heart rate is then subtracted from this number. The answer is then multiplied by the target percent (50% for example) and the product is added back to resting heart rate to provide the target exercise session heart rate. Intensity will be increased by 5% every week (as tolerated by the participant) to a maximum of 80% of maximal heart rate. Exercise time will progress from an initial 20 minutes per session to a maximum of 45 minutes by increasing 5 minutes each week.

Intervention type: OTHER
Group type: ACTIVE_COMPARATOR
Intervention: Exercise training
Description: Participants will exercise 3 times a week on a stationary ergometer. Exercise intensity will begin at low levels (50% of maximal heart rate reserve) calculated utilizing the Karvonen method. Briefly, target exercise heart rate (HR) is calculated by subtracting the persons age from 220. Resting heart rate is then subtracted from this number. The answer is then multiplied by the target percent (50% for example) and the product is added back to resting heart rate to provide the target exercise session heart rate. Intensity will be increased by 5% every week (as tolerated by the participant) to a maximum of 80% of maximal heart rate. Exercise time will progress from an initial 20 minutes per session to a maximum of 45 minutes by increasing 5 minutes each week.