Trial Outcomes & Findings for Systemic Sclerosis (SSc) Vasculopathy: Improved Clinical Monitoring and Treatment (NCT NCT02530996)
NCT ID: NCT02530996
Last Updated: 2021-04-05
Results Overview
FMD diameter of artery (mm, higher better)
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
12 participants
Primary outcome timeframe
FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day washout period.
Results posted on
2021-04-05
Participant Flow
156 patients were enrolled and screened in IRB 38705 during the funding period 01/01/2016 - 12/31/2020 in SSc clinic, but only 12 participated in a controlled, counter-balanced, double-blind, crossover experimental design with two conditions, BH4 and placebo IRB 40212 in the Utah Vascular Research Laboratory at the Salt Lake VAMC.
While 32 participants were intended, this study was concluded after 12 participants due to budgetary restrictions.
Participant milestones
| Measure |
6 SSc Patients Received BH4 Then Placebo
Prior to January 18, 2017, a controlled, counter-balanced, double-blind, crossover experimental design with two conditions, BH4 and placebo, was employed. There was a washout period of at least 5 days before crossing over into the alternate condition.
|
6 SSc Patients Received Placebo Then BH4
Prior to January 18, 2017, a controlled, counter-balanced, double-blind, crossover experimental design with two conditions, BH4 and placebo, was employed. There was a washout period of at least 5 days before crossing over into the alternate condition.
|
|---|---|---|
|
First Intervention
STARTED
|
6
|
6
|
|
First Intervention
COMPLETED
|
6
|
6
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
|
Washout (5 Days)
STARTED
|
6
|
6
|
|
Washout (5 Days)
COMPLETED
|
6
|
6
|
|
Washout (5 Days)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention
STARTED
|
6
|
6
|
|
Second Intervention
COMPLETED
|
6
|
6
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Systemic Sclerosis (SSc) Vasculopathy: Improved Clinical Monitoring and Treatment
Baseline characteristics by cohort
| Measure |
12 SSc Patients Received BH4 and Placebo
n=12 Participants
12 SSc received BH4 intervention (blinded) and placebo in a cross-over design.
Patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design
Vasculopathy assessment: Non-invasive technique, flow mediated dilatation (FMD) to define vasculopathy in SSc.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day washout period.FMD diameter of artery (mm, higher better)
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Flow Mediated Dilatation (FMD)-Diameter of Artery
|
3.79 mm
Standard Error 0.20
|
3.78 mm
Standard Error 0.21
|
PRIMARY outcome
Timeframe: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.Population: Twelve patients with SSc had FMD parameters quantified after cuff at baseline, after placebo, and after BH4. FMD is expressed as a percent increase in diameter from baseline.
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Flow Mediated Dilatation-shear Rate
|
95 sec^-1
Standard Error 12
|
100 sec^-1
Standard Error 13
|
PRIMARY outcome
Timeframe: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.Population: Twelve patients with SSc had FMD parameters quantified after cuff at baseline, after placebo, and after BH4. FMD is expressed as a percent increase in diameter from baseline.
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Flow Mediated Dilatation- Blood Velocity
|
4.4 cm/sec
Standard Error 0.6
|
4.5 cm/sec
Standard Error 0.4
|
PRIMARY outcome
Timeframe: FMD was obtained on a single day at two different time points (after placebo and intervention) after a 5 day wash out period.Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Flow Mediated Dilatation-blood Flow
|
32 ml/min
Standard Error 7
|
30 ml/min
Standard Error 3
|
SECONDARY outcome
Timeframe: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.MDA (lower better). Plasma malondialdehyde assessed by Oxis Research/Percipio Bioscience, Foster City, CA.
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Oxidative Stress Measurement-MDA: Malondialdehyde
|
2.8 uM
Standard Error 0.1
|
2.9 uM
Standard Error 0.2
|
SECONDARY outcome
Timeframe: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.CAT (higher better) assessed by Cayman Chemical Company, Ann Arbor, MI.
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Oxidative Stress Measurement-catalase (CAT)
|
86 nM/min/mL
Standard Error 7
|
78 nM/min/mL
Standard Error 11
|
SECONDARY outcome
Timeframe: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.Protein carbonyl (lower better). Plasma protein carbonyl levels assessed by Northwest Life Science Specialties, LLC Vancouver, WA.
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Oxidative Stress Measurement- Protein Carbonyl
|
0.17 nM/mg
Standard Error 0.01
|
0.16 nM/mg
Standard Error 0.01
|
SECONDARY outcome
Timeframe: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.FRAP (higher better). FRAP assessed using the method described by Benzie and Strain.
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Oxidative Stress Measurement- Ferric Reducing Ability of Plasma (FRAP)
|
1.8 nM/L
Standard Error 0.1
|
1.8 nM/L
Standard Error 0.2
|
SECONDARY outcome
Timeframe: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.SOD (higher better). SOD assessed by Cayman Chemical Company, Ann Arbor, MI.
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Oxidative Stress Measurement- Superoxide Dismutase (SOD)
|
10.7 U/mL
Standard Error 0.6
|
11.1 U/mL
Standard Error 1.3
|
SECONDARY outcome
Timeframe: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.IL-6 (lower better), assessed by R\&D Systems, Minneapolis, MN.
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Oxidative Stress Measurement- Interleukin 6 (IL-6)
|
1.3 pg/mL
Standard Error 0.5
|
1.4 pg/mL
Standard Error 0.5
|
SECONDARY outcome
Timeframe: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.TNF-α (lower better), assessed by R\&D Systems, Minneapolis, MN.
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Oxidative Stress Measurement- Tumor Necrosis Factor Alpha (TNF-α,
|
1.1 pg/mL
Standard Error 0.2
|
1.3 pg/mL
Standard Error 0.2
|
SECONDARY outcome
Timeframe: Oxidative stress measurements were obtained on a single day at two different time points (after placebo and intervention) after a 5-day wash out period.CRP (lower better). CRP assessed by R\&D Systems, Minneapolis, MN.
Outcome measures
| Measure |
12 SSc Participants With Placebo
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
12 Participants With BH4
n=12 Participants
12 patients were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.
|
|---|---|---|
|
Oxidative Stress Measurement- C-reactive Protein (CRP)
|
3.2 mg/L
Standard Error 0.7
|
3.1 mg/L
Standard Error 0.6
|
Adverse Events
12 SSc Participants Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
12 SSc Participants BH4
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place