Raynaud
Conditions
Keywords
Secondary Raynaud's Phenomenon
Brief summary
The investigators propose that tadalafil will increase digital blood flow and improve the symptoms and signs of secondary Raynaud's phenomenon.
Detailed description
The primary goal of our study is to decrease the frequency, duration and severity of vasospastic attacks in patients with secondary Raynaud's. The secondary goal is to document increased blood flow and lessened capillary dysfunction in these patients. Both of these goals are to be achieved using a course of treatment with Tadalafil.We anticipate a decrease in the frequency, duration and severity of Raynaud's attacks. Improved digital blood flow and digital blood pressures, and a decrease in digital capillary dysfunction.
Interventions
DRUGTadalafil
Subjects will be randomized to receive either tadalafil for the first month followed by placebo or placebo for the first month and followed by tadalafil
Sponsors
Eli Lilly and Company
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* active Raynaud's Phenomenon * stable disease and medication requirements over the previous 2 months * subjects willing and able to participate in study assessments * ability to understand and sign informed consent * ages 18 to 65, both sexes * a diagnosis of diffuse or limited cutaneous sclerosis, MCTD using the American College Rheumatology criteria
Exclusion criteria
* uncontrolled HTN, DM, unstable disease, angina or using oral nitrates * smoking, active alcoholism, drug abuse within 5 years * abnormal renal function * ulnar arterial occlusive disease as shown by a positive Allen Test * Pregnant or breast feeding or considering preg. in next 4 months * past or present major psych. illness * allergy or sensitivity to tadalafil * subject unable to understand protocol or give informed consent * part. in another study trial within 30 days * taking sildenafil
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Raynaud's Phenomenon Attacks Per Day | 9 weeks | Subjects kept a daily record of the number of Raynaud's phenomenon attacks they experienced per day. Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment. |
| Duration of Raynaud's Phenomenon Attacks | 9 weeks | Subjects kept a daily record of the number of Raynaud's phenomenon attacks they experienced per day and the duration of each attack. Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment. |
| Raynaud Severity Visual Analog Score (VAS) | 9 weeks | The VAS is a 100 millimeter (mm) line where 0 mm (left boundary) represents Raynaud's disease of low severity, and 100 mm (right boundary) represents extremely severe Raynaud's disease. The subject makes a vertical mark on the VAS to indicate the severity of Raynaud's disease over the past two weeks. The Raynaud's severity score is the distance from the left boundary to the vertical mark in mm. Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment. |
| Raynaud's Condition Score (RCS) Visual Analog Scale (VAS) | 9 weeks | The VAS is a 100 millimeter (mm) line where 0 mm (left boundary) represents no difficulty with Raynaud's disease, and 100 mm (right boundary) represents extreme difficulty with Raynaud's disease. The subject makes a vertical mark on the VAS to indicate difficulty experienced that day with Raynaud's disease. The RCS is the distance from the left boundary to the vertical mark in mm. Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Digital Blood Pressure | 9 weeks | Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment. |
| Capillary Diameter | 9 weeks | Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tadalafil Followed by Placebo Subjects received tadalafil 20 mg every other day for four weeks followed by placebo every other day for four weeks. A one week washout occurred between the treatment and placebo periods. | 5 |
| Placebo Followed by Tadalafil Subjects received placebo every other day for four weeks, followed by tadalafil 20 mg every other day for four weeks. A one week washout occurred between the placebo and treatment periods. | 5 |
| Total | 10 |
Baseline characteristics
| Characteristic | Tadalafil Followed by Placebo | Placebo Followed by Tadalafil | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
Duration of Raynaud's Phenomenon Attacks
Subjects kept a daily record of the number of Raynaud's phenomenon attacks they experienced per day and the duration of each attack. Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment.
Time frame: 9 weeks
Population: Two of the ten enrolled subjects were excluded from analysis: one subject due to early withdrawal, and a second subject to avoid bias due to bilateral subclavian stent placement midway through the study. For subject 2, Week 5 data was used for both Pre-treatment and Pre-placebo because Baseline/Week 0 visit data was not obtained.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pre-treatment | Duration of Raynaud's Phenomenon Attacks | 5.7 minutes |
| Week 4 of Treatment | Duration of Raynaud's Phenomenon Attacks | 11.4 minutes |
| Pre-placebo | Duration of Raynaud's Phenomenon Attacks | 1.2 minutes |
| Week 4 of Placebo | Duration of Raynaud's Phenomenon Attacks | 14.2 minutes |
Primary
Number of Raynaud's Phenomenon Attacks Per Day
Subjects kept a daily record of the number of Raynaud's phenomenon attacks they experienced per day. Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment.
Time frame: 9 weeks
Population: Two of the ten enrolled subjects were excluded from analysis: one subject due to early withdrawal, and a second subject to avoid bias due to bilateral subclavian stent placement midway through the study. For subject 2, Week 5 data was used for both Pre-treatment and Pre-placebo because Baseline/Week 0 visit data was not obtained.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pre-treatment | Number of Raynaud's Phenomenon Attacks Per Day | 2.4 Raynaud's attacks per day |
| Week 4 of Treatment | Number of Raynaud's Phenomenon Attacks Per Day | 1.1 Raynaud's attacks per day |
| Pre-placebo | Number of Raynaud's Phenomenon Attacks Per Day | 2.0 Raynaud's attacks per day |
| Week 4 of Placebo | Number of Raynaud's Phenomenon Attacks Per Day | 2.3 Raynaud's attacks per day |
Primary
Raynaud's Condition Score (RCS) Visual Analog Scale (VAS)
The VAS is a 100 millimeter (mm) line where 0 mm (left boundary) represents no difficulty with Raynaud's disease, and 100 mm (right boundary) represents extreme difficulty with Raynaud's disease. The subject makes a vertical mark on the VAS to indicate difficulty experienced that day with Raynaud's disease. The RCS is the distance from the left boundary to the vertical mark in mm. Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment.
Time frame: 9 weeks
Population: Two of the ten enrolled subjects were excluded from analysis: one subject due to early withdrawal, and a second subject to avoid bias due to bilateral subclavian stent placement midway through the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pre-treatment | Raynaud's Condition Score (RCS) Visual Analog Scale (VAS) | 38.5 millimeters |
| Week 4 of Treatment | Raynaud's Condition Score (RCS) Visual Analog Scale (VAS) | 9 millimeters |
| Pre-placebo | Raynaud's Condition Score (RCS) Visual Analog Scale (VAS) | 35 millimeters |
| Week 4 of Placebo | Raynaud's Condition Score (RCS) Visual Analog Scale (VAS) | 26 millimeters |
Primary
Raynaud Severity Visual Analog Score (VAS)
The VAS is a 100 millimeter (mm) line where 0 mm (left boundary) represents Raynaud's disease of low severity, and 100 mm (right boundary) represents extremely severe Raynaud's disease. The subject makes a vertical mark on the VAS to indicate the severity of Raynaud's disease over the past two weeks. The Raynaud's severity score is the distance from the left boundary to the vertical mark in mm. Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment.
Time frame: 9 weeks
Population: Two of the ten enrolled subjects were excluded from analysis: one subject due to early withdrawal, and a second subject to avoid bias due to bilateral subclavian stent placement midway through the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pre-treatment | Raynaud Severity Visual Analog Score (VAS) | 39 millimeters |
| Week 4 of Treatment | Raynaud Severity Visual Analog Score (VAS) | 16.5 millimeters |
| Pre-placebo | Raynaud Severity Visual Analog Score (VAS) | 51.5 millimeters |
| Week 4 of Placebo | Raynaud Severity Visual Analog Score (VAS) | 37 millimeters |
Secondary
Capillary Diameter
Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment.
Time frame: 9 weeks
Population: Two of the ten enrolled subjects were excluded from analysis: one subject due to early withdrawal, and a second subject to avoid bias due to bilateral subclavian stent placement midway through the study. For subject 8, Baseline/Week 0 data was used for both Pre-treatment and Pre-placebo, and Week 2 data was used for Week 4 of placebo.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pre-treatment | Capillary Diameter | 9.3 micrometers |
| Week 4 of Treatment | Capillary Diameter | 10 micrometers |
| Pre-placebo | Capillary Diameter | 10.7 micrometers |
| Week 4 of Placebo | Capillary Diameter | 10 micrometers |
Secondary
Digital Blood Pressure
Results are reported from data collected at Baseline/Week 0, Week 4, Week 5, and Week 9 visits. In subjects receiving tadalafil followed by placebo: Baseline/Week 0 data is Pre-treatment, Week 4 data corresponds to Week 4 of treatment, Week 5 data is Pre-placebo, and Week 9 data corresponds to Week 4 of placebo. In subjects receiving placebo followed by tadalafil: Baseline/Week 0 data is Pre-placebo, Week 4 data corresponds to Week 4 of placebo, Week 5 data is Pre-treatment, and Week 9 data corresponds to Week 4 of treatment.
Time frame: 9 weeks
Population: Two of the ten enrolled subjects were excluded from analysis: one subject due to early withdrawal, and a second subject to avoid bias due to bilateral subclavian stent placement midway through the study. For subject 10, Week 2 data was used for Week 4 of placebo because digital blood pressure data was not obtained at the Week 4 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pre-treatment | Digital Blood Pressure | 97 mm Hg |
| Week 4 of Treatment | Digital Blood Pressure | 80 mm Hg |
| Pre-placebo | Digital Blood Pressure | 84 mm Hg |
| Week 4 of Placebo | Digital Blood Pressure | 80 mm Hg |