Trial Outcomes & Findings for Vascular Dysfunction in Black Individuals: Roles of Nitric Oxide and Endothelin-1 (NCT NCT04770155)

Last Updated: 2023-10-31

Results Overview

The percent change in arterial diameter normalized to arterial shear rate during reperfusion after 5 minutes of circulatory occlusion.

Recruitment status

TERMINATED

Study phase

EARLY_PHASE1

Target enrollment

8 participants

Primary outcome timeframe

Within 4 hours of drug/supplement administration.

Results posted on

2023-10-31

Participant Flow

Participant milestones

Participant milestones
Measure	Experimental: Beetroot Juice, Then Placebo (Aim 1a) Upon arriving at the laboratory, participants will ingest 140 ml of beetroot juice containing a high (\~12.8 mmol) concentration of nitrates (James White Drinks, Suffolk, UK), or 140 ml of beetroot juice containing a low concentration (\~0.0055 mmol) of nitrates (James White Drinks, Suffolk, UK). Dietary Nitrates 400 mg: The nitrates in the beetroot juice will be absorbed and reduced in the plasma to nitrite and nitric oxide, increasing endothelium-independent nitric oxide bioavailability.	Experimental: Placebo, Then Beetroot Juice (Aim 1a) Upon arriving at the laboratory, participants will ingest 140 ml of beetroot juice containing a low concentration (\~0.0055 mmol) of nitrates (James White Drinks, Suffolk, UK), or 140 ml of beetroot juice containing a high (\~12.8 mmol) concentration of nitrates (James White Drinks, Suffolk, UK). Dietary Nitrates 400 mg: The nitrates in the beetroot juice will be absorbed and reduced in the plasma to nitrite and nitric oxide, increasing endothelium-independent nitric oxide bioavailability.	Experimental: L-citrulline, Then Placebo (Aim 1b) Participants will receive pills containing 3 g of L-citrulline (Superior Labs, Park City, UT) to take twice daily for 7 days before the study visit, or pills containing a placebo to take twice daily for 7 days before the study visit. L-citrulline 3 g: Ingested L-citrulline becomes available in large quantities in the plasma for enzymatic conversion into L-arginine. The activity of the endothelial nitric oxide synthase converts L-arginine into nitric oxide, increasing endothelium-dependent nitric oxide bioavailability.	Experimental: Placebo, Then L-citrulline (Aim 1b) Participants will receive pills containing a placebo to take twice daily for 7 days before the study visit, or pills containing 3 g of L-citrulline (Superior Labs, Park City, UT) to take twice daily for 7 days before the study visit. L-citrulline 3 g: Ingested L-citrulline becomes available in large quantities in the plasma for enzymatic conversion into L-arginine. The activity of the endothelial nitric oxide synthase converts L-arginine into nitric oxide, increasing endothelium-dependent nitric oxide bioavailability.	Experimental: Sildenafil, Then Placebo (Aim 1c) Upon arriving at the laboratory, participants will ingest a liquid mixture containing Sildenafil (100 mg), an inhibitor of phosphodiesterase 5, or a liquid mixture containing a placebo. Sildenafil 100 mg: Sildenafil inhibits phosphodiesterase 5, an enzyme that degrades cyclic guanosine monophosphate in the vascular smooth muscle cells inactivating the nitric oxide-mediated signal; thus, Sildenafil will prolong the availability of cyclic guanosine monophosphate, enhancing the nitric oxide-mediated intracellular cascade.	Experimental: Placebo, Then Sildenafil (Aim 1c) Upon arriving at the laboratory, participants will ingest a liquid mixture containing a placebo, or a liquid mixture containing Sildenafil (100 mg), an inhibitor of phosphodiesterase 5. Sildenafil 100 mg: Sildenafil inhibits phosphodiesterase 5, an enzyme that degrades cyclic guanosine monophosphate in the vascular smooth muscle cells inactivating the nitric oxide-mediated signal; thus, Sildenafil will prolong the availability of cyclic guanosine monophosphate, enhancing the nitric oxide-mediated intracellular cascade.	Experimental: Bosentan, Then Placebo (Aim 2) Upon arriving at the laboratory, participants will ingest a liquid mixture containing Bosentan (125 mg), a non-selective blocker of endothelin-1 receptors ETA and ETB, or a liquid mixture containing a placebo. Bosentan 125 mg: Bosentan blocks endothelin-1 receptors ETA and ETB, leading to a reduction in vasoconstrictor tone and a greater magnitude of vasodilator responses.	Experimental: Placebo, Then Bosentan (Aim 2) Upon arriving at the laboratory, participants will ingest a liquid mixture containing a placebo, or a liquid mixture containing Bosentan (125 mg), a non-selective blocker of endothelin-1 receptors ETA and ETB. Bosentan 125 mg: Bosentan blocks endothelin-1 receptors ETA and ETB, leading to a reduction in vasoconstrictor tone and a greater magnitude of vasodilator responses.
Overall Study STARTED	1	1	1	1	1	1	1	1
Overall Study COMPLETED	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	1	1	1	1	1	1	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental: Beetroot Juice, Then Placebo (Aim 1a) Upon arriving at the laboratory, participants will ingest 140 ml of beetroot juice containing a high (\~12.8 mmol) concentration of nitrates (James White Drinks, Suffolk, UK), or 140 ml of beetroot juice containing a low concentration (\~0.0055 mmol) of nitrates (James White Drinks, Suffolk, UK). Dietary Nitrates 400 mg: The nitrates in the beetroot juice will be absorbed and reduced in the plasma to nitrite and nitric oxide, increasing endothelium-independent nitric oxide bioavailability.	Experimental: Placebo, Then Beetroot Juice (Aim 1a) Upon arriving at the laboratory, participants will ingest 140 ml of beetroot juice containing a low concentration (\~0.0055 mmol) of nitrates (James White Drinks, Suffolk, UK), or 140 ml of beetroot juice containing a high (\~12.8 mmol) concentration of nitrates (James White Drinks, Suffolk, UK). Dietary Nitrates 400 mg: The nitrates in the beetroot juice will be absorbed and reduced in the plasma to nitrite and nitric oxide, increasing endothelium-independent nitric oxide bioavailability.	Experimental: L-citrulline, Then Placebo (Aim 1b) Participants will receive pills containing 3 g of L-citrulline (Superior Labs, Park City, UT) to take twice daily for 7 days before the study visit, or pills containing a placebo to take twice daily for 7 days before the study visit. L-citrulline 3 g: Ingested L-citrulline becomes available in large quantities in the plasma for enzymatic conversion into L-arginine. The activity of the endothelial nitric oxide synthase converts L-arginine into nitric oxide, increasing endothelium-dependent nitric oxide bioavailability.	Experimental: Placebo, Then L-citrulline (Aim 1b) Participants will receive pills containing a placebo to take twice daily for 7 days before the study visit, or pills containing 3 g of L-citrulline (Superior Labs, Park City, UT) to take twice daily for 7 days before the study visit. L-citrulline 3 g: Ingested L-citrulline becomes available in large quantities in the plasma for enzymatic conversion into L-arginine. The activity of the endothelial nitric oxide synthase converts L-arginine into nitric oxide, increasing endothelium-dependent nitric oxide bioavailability.	Experimental: Sildenafil, Then Placebo (Aim 1c) Upon arriving at the laboratory, participants will ingest a liquid mixture containing Sildenafil (100 mg), an inhibitor of phosphodiesterase 5, or a liquid mixture containing a placebo. Sildenafil 100 mg: Sildenafil inhibits phosphodiesterase 5, an enzyme that degrades cyclic guanosine monophosphate in the vascular smooth muscle cells inactivating the nitric oxide-mediated signal; thus, Sildenafil will prolong the availability of cyclic guanosine monophosphate, enhancing the nitric oxide-mediated intracellular cascade.	Experimental: Placebo, Then Sildenafil (Aim 1c) Upon arriving at the laboratory, participants will ingest a liquid mixture containing a placebo, or a liquid mixture containing Sildenafil (100 mg), an inhibitor of phosphodiesterase 5. Sildenafil 100 mg: Sildenafil inhibits phosphodiesterase 5, an enzyme that degrades cyclic guanosine monophosphate in the vascular smooth muscle cells inactivating the nitric oxide-mediated signal; thus, Sildenafil will prolong the availability of cyclic guanosine monophosphate, enhancing the nitric oxide-mediated intracellular cascade.	Experimental: Bosentan, Then Placebo (Aim 2) Upon arriving at the laboratory, participants will ingest a liquid mixture containing Bosentan (125 mg), a non-selective blocker of endothelin-1 receptors ETA and ETB, or a liquid mixture containing a placebo. Bosentan 125 mg: Bosentan blocks endothelin-1 receptors ETA and ETB, leading to a reduction in vasoconstrictor tone and a greater magnitude of vasodilator responses.	Experimental: Placebo, Then Bosentan (Aim 2) Upon arriving at the laboratory, participants will ingest a liquid mixture containing a placebo, or a liquid mixture containing Bosentan (125 mg), a non-selective blocker of endothelin-1 receptors ETA and ETB. Bosentan 125 mg: Bosentan blocks endothelin-1 receptors ETA and ETB, leading to a reduction in vasoconstrictor tone and a greater magnitude of vasodilator responses.
Overall Study Baseline measurements only. Investigator did not obtain treatments for the planned interventions.	1	1	1	1	1	1	1	1

Baseline Characteristics

Vascular Dysfunction in Black Individuals: Roles of Nitric Oxide and Endothelin-1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: Beetroot Juice, Then Placebo (Aim 1a) n=1 Participants Upon arriving at the laboratory, participants will ingest 140 ml of beetroot juice containing a high (\~12.8 mmol) concentration of nitrates (James White Drinks, Suffolk, UK), or 140 ml of beetroot juice containing a low concentration (\~0.0055 mmol) of nitrates (James White Drinks, Suffolk, UK). Dietary Nitrates 400 mg: The nitrates in the beetroot juice will be absorbed and reduced in the plasma to nitrite and nitric oxide, increasing endothelium-independent nitric oxide bioavailability.	Experimental: Placebo, Then Beetroot Juice (Aim 1a) n=1 Participants Upon arriving at the laboratory, participants will ingest 140 ml of beetroot juice containing a low concentration (\~0.0055 mmol) of nitrates (James White Drinks, Suffolk, UK), or 140 ml of beetroot juice containing a high (\~12.8 mmol) concentration of nitrates (James White Drinks, Suffolk, UK). Dietary Nitrates 400 mg: The nitrates in the beetroot juice will be absorbed and reduced in the plasma to nitrite and nitric oxide, increasing endothelium-independent nitric oxide bioavailability.	Experimental: L-citrulline, Then Placebo (Aim 1b) n=1 Participants Participants will receive pills containing 3 g of L-citrulline (Superior Labs, Park City, UT) to take twice daily for 7 days before the study visit, or pills containing a placebo to take twice daily for 7 days before the study visit. L-citrulline 3 g: Ingested L-citrulline becomes available in large quantities in the plasma for enzymatic conversion into L-arginine. The activity of the endothelial nitric oxide synthase converts L-arginine into nitric oxide, increasing endothelium-dependent nitric oxide bioavailability.	Experimental: Placebo, Then L-citrulline (Aim 1b) n=1 Participants Participants will receive pills containing a placebo to take twice daily for 7 days before the study visit, or pills containing 3 g of L-citrulline (Superior Labs, Park City, UT) to take twice daily for 7 days before the study visit. L-citrulline 3 g: Ingested L-citrulline becomes available in large quantities in the plasma for enzymatic conversion into L-arginine. The activity of the endothelial nitric oxide synthase converts L-arginine into nitric oxide, increasing endothelium-dependent nitric oxide bioavailability.	Experimental: Sildenafil, Then Placebo (Aim 1c) n=1 Participants Upon arriving at the laboratory, participants will ingest a liquid mixture containing Sildenafil (100 mg), an inhibitor of phosphodiesterase 5, or a liquid mixture containing a placebo. Sildenafil 100 mg: Sildenafil inhibits phosphodiesterase 5, an enzyme that degrades cyclic guanosine monophosphate in the vascular smooth muscle cells inactivating the nitric oxide-mediated signal; thus, Sildenafil will prolong the availability of cyclic guanosine monophosphate, enhancing the nitric oxide-mediated intracellular cascade.	Experimental: Placebo, Then Sildenafil (Aim 1c) n=1 Participants Upon arriving at the laboratory, participants will ingest a liquid mixture containing a placebo, or a liquid mixture containing Sildenafil (100 mg), an inhibitor of phosphodiesterase 5. Sildenafil 100 mg: Sildenafil inhibits phosphodiesterase 5, an enzyme that degrades cyclic guanosine monophosphate in the vascular smooth muscle cells inactivating the nitric oxide-mediated signal; thus, Sildenafil will prolong the availability of cyclic guanosine monophosphate, enhancing the nitric oxide-mediated intracellular cascade.	Experimental: Bosentan, Then Placebo (Aim 2) n=1 Participants Upon arriving at the laboratory, participants will ingest a liquid mixture containing Bosentan (125 mg), a non-selective blocker of endothelin-1 receptors ETA and ETB, or a liquid mixture containing a placebo. Bosentan 125 mg: Bosentan blocks endothelin-1 receptors ETA and ETB, leading to a reduction in vasoconstrictor tone and a greater magnitude of vasodilator responses.	Experimental: Placebo, Then Bosentan (Aim 2) n=1 Participants Upon arriving at the laboratory, participants will ingest a liquid mixture containing a placebo, or a liquid mixture containing Bosentan (125 mg), a non-selective blocker of endothelin-1 receptors ETA and ETB. Bosentan 125 mg: Bosentan blocks endothelin-1 receptors ETA and ETB, leading to a reduction in vasoconstrictor tone and a greater magnitude of vasodilator responses.	Total n=8 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=113 Participants	1 Participants n=163 Participants	1 Participants n=160 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants	1 Participants n=8 Participants	8 Participants n=8 Participants
Age, Categorical >=65 years	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Sex: Female, Male Female	1 Participants n=113 Participants	1 Participants n=163 Participants	1 Participants n=160 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=8 Participants	3 Participants n=8 Participants
Sex: Female, Male Male	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants	1 Participants n=8 Participants	5 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=8 Participants	1 Participants n=8 Participants
Race (NIH/OMB) White	1 Participants n=113 Participants	1 Participants n=163 Participants	1 Participants n=160 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	1 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=8 Participants	7 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants
Region of Enrollment United States	1 participants n=113 Participants	1 participants n=163 Participants	1 participants n=160 Participants	1 participants n=483 Participants	1 participants n=36 Participants	1 participants n=10 Participants	1 participants n=115 Participants	1 participants n=8 Participants	8 participants n=8 Participants

PRIMARY outcome

Timeframe: Within 4 hours of drug/supplement administration.

Population: Flow-mediated dilation was not collected in any participant.

The percent change in arterial diameter normalized to arterial shear rate during reperfusion after 5 minutes of circulatory occlusion.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Within 4 hours of drug/supplement administration.

Population: Reactive hyperemia with cuff release was not collected in any participant.

Blood velocity area-under-the-curve from the beginning of reperfusion to return to resting values.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Within 4 hours of drug/supplement administration.

Population: Muscle hyperemia with passive leg movement was not collected in any participant.

Peak and the area-under-the-curve of the change in femoral artery blood flow during 1 minute of passive leg movement.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline measurements with no drug/supplement administration before or after.

Population: The only data collected were baseline measurements and no participants were ever given either intervention; the investigator was never able to obtain the treatments to use for the planned intervention arm of the study, resulting in its termination. Upon resigning his Instructor position at UMMC, the investigator backed up the baseline data files on an external hard drive. Unfortunately, some issues with the external hard drive corrupted the files, making them no longer accessible.

Changes in brachial artery blood flow and conductance during single handgrip contractions at 3 intensities.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Within 4 hours of drug/supplement administration.

Population: Muscle hyperemia with rhythmic knee extension exercise was not collected in any participant.

Changes in femoral artery blood flow and conductance during 3 minutes of rhythmic knee extension exercise.