SclerodermaPhase 2TAMERNCT02370784
Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma
A Phase 2 study testing atorvastatin in people with Scleroderma, run by Robyn T. Domsic, MD, MPH at 1 site in United States.
Trial summary
The purpose of this study is to learn about the effect atorvastatin on blood vessel function and Raynaud symptoms in patients with early diffuse systemic sclerosis. Systemic sclerosis is a disease characterized by blood vessel injury, immune system activation and fibrosis. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Scleroderma
- What is being tested?
- atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2015to 15 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- early diffuse scleroderma (< 3 years from the first scleroderma-related symptom)
- Raynaud phenomenon
- no use of lipid-lowering medication within 60 days
Who cannot join
- pregnancy
- renal or kidney dysfunction (creatinine < 2.0 mg/dL or creatinine clearance < 60 c/min)
- diabetes mellitus
- known cardiovascular disease or a prior history of stroke
- history of liver disease
- new or changed dose of calcium channel blockers (CCB) and angiotensin receptor blockers (ARBs) in the last 4 weeks
- known allergy or adverse reaction to the atorvastatin or another statin drug
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
About this study
Official title: The Effect of Atorvastatin on Microvascular Endothelial Function and Raynaud in Early Diffuse Systemic Sclerosis
The purpose of this study is to learn about the effect atorvastatin on blood vessel function and Raynaud symptoms in patients with early diffuse systemic sclerosis.
Systemic sclerosis is a disease characterized by blood vessel injury, immune system activation and fibrosis. Blood vessel injury is thought to be important early in the disease. Blood vessel complications of systemic sclerosis include Raynaud phenomena, finger and toe ulcers, and pulmonary hypertension. While atorvastatin reduces cholesterol, it is recognized to have many effects beyond cholesterol reduction. These include improvement of blood vessel function and reduction of fibrosis. We hypothesize that treatment with atorvastatin over 16 weeks will improve blood vessel function and Raynaud symptom in patients with early diffuse systemic sclerosis. We hope that by targeting therapy early in the disease we may delay blood vessel changes and improve Raynaud symptoms.
Read the detailed description
Systemic sclerosis (SSc) is a multisystem autoimmune illness characterized by vasculopathy, immune system activation and fibrosis of the skin and internal organs. SSc affects approximately 240 people per million in the US, but is a disease for which there is no FDA approved medication. Current hypothesis of pathogenesis suggest that a vascular injury with endothelial dysfunction may be an inciting event contributing to immunologic activation and fibrosis in the pathogenesis of the disease. More than 90% of individuals with SSc have vascular complications including Raynaud phenomenon, digital ulcers or gangrene and pulmonary hypertension; with microvascular abnormalities felt to contribute to Raynaud and digital ulcerations.
Statin medications are well-recognized to have pleiotropic effects which may modify all three aspects of SSc pathogenesis. Early diagnosis and treatment of microvascular endothelial dysfunction and Raynaud phenomeonan may have the greatest effect in early disease. Thus, we hypothesize that treatment with atorvastatin in a well-defined cohort of early diffuse systemic sclerosis will produce beneficial results.
Participants will be patients with early diffuse systemic sclerosis and Raynaud phenomenon who have no history of cardiovascular disease or diabetes. A total of 30 patients will be enrolled and followed for 16 weeks. Half the patients will be randomized to atorvastatin and half to placebo. Patients will be allowed to continue underlying immunosuppressive and Raynaud therapy at stable doses during the trial. Since this is a pilot study, future larger controlled trials will be necessary to clearly demonstrate drug effectiveness. Investigators are hoping that this study will give us signals to guide a future multicenter clinical trial.
- Conditions
- Scleroderma
- Being tested
- atorvastatin, Placebo
- Keywords
- early diffuse scleroderma, Raynaud
- Medical subject headings
- Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atorvastatinDrug
Also called Lipitor
Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.
PlaceboDrug
oral drug of similar appearance to atorvastatin
| Study group | Role | What they receive |
|---|---|---|
| Active Drug | Active comparator | atorvastatin 40 mg once daily for sixteen weeks Receives: Drug: atorvastatin |
| Placebo control | Placebo comparator | receive a placebo of similar appearance once daily for sixteen weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients Improving Their EndoPAT Reactive Hyperemia Index (RHI) at the End-of-study (16 Weeks)
EndoPAT is a proprietary device that assesses digital (microvascular) endothelial function during reactive hyperemia. A probe is placed on both index fingers. After 5 minutes of baseline observation, one arm is occluded for 5 minutes, while the other is not and serves as control. Output is the reactive hyperemia index (RHI), calculated as the post-to-pre occlusion signal ratio in the occluded side, "normalized to the control side and further corrected for baseline vascular tone" per Itamar Medical. There are no units. RHI ≤ 1.67 is abnormal and indicates endothelial dysfunction.
Measured: Change in RHI from baseline to 16 weeks expressed as the percentage of patients who improve (respond).
Secondary outcomes (3)
Change in the Raynaud Condition Score (RCS) at 16 Weeks (End-of-study) From Baseline
The Raynaud Condition Score is a patient-reported outcome of a single question regarding Raynaud severity. It is a visual analog scale with a results range of 0-100. A score of 0 us is no symptoms, and 100 severe symptoms. It is recommended by OMERACT for assessment of Raynaud phenomenon.
Measured: change in RCS from baseline to week 16
The Median Change in the Raynaud Phenomenon Visual Analog Scale (RP-VAS) Score at 16 Weeks (End-of-study) Compared to Baseline in the Atorvastatin and Placebo Groups.
The RP-VAS scale measure ranges from 0-100, with 0 being no symptoms and 100 severe symptoms. Reported is the median and interquartile range of change between baseline and week 16 (end-of-study).
Measured: baseline to 16 weeks
% of Patients Who Improved Their Brachial Flow-mediation Dilation (%FMD) at 16 Weeks
%FMD = change in brachial artery flow-mediation dilation between pre and post-ischemia. Baseline (pre-ischemia) is the reference to which percentage change is calculated.
Result is expressed as the % of patients who had an improvement in their %FMD at 16 weeks compared to baseline.
Measured: baseline to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2015 (estimated)
- Study startFeb 2015
- Primary completion15 Dec 2018
- Study completion15 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SclerodermaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Robyn T. Domsic, MD, MPH
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor-investigator, Robyn T. Domsic, MD, MPH, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02370784
- Sponsor's protocol ID
- PRO14010170
- Other IDs
- 1R21AR066305-01A1
- Acronym
- TAMER
- Status last verified
- Aug 2020
- First submitted
- 26 Jan 2015
- Last updated
- 12 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Atorvastatin on Microvascular Endothelial Function and Raynaud in Early Diffuse Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT02370784
- Acronym / sponsor ID
- TAMER / PRO14010170
- Conditions
- Scleroderma
- Keywords
- early diffuse scleroderma, Raynaud
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Robyn T. Domsic, MD, MPHUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- Feb 2015
- Primary completion
- 15 Dec 2018 (actual)
- Study completion
- 15 Dec 2019 (actual)
- First posted
- 25 Feb 2015 (estimated)
- Results
- Posted 12 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn about the effect atorvastatin on blood vessel function and Raynaud symptoms in patients with early diffuse systemic sclerosis.
Systemic sclerosis is a disease characterized by blood vessel injury, immune system activation and fibrosis. Blood vessel injury is thought to be important early in the disease. Blood vessel complications of systemic sclerosis include Raynaud phenomena, finger and toe ulcers, and pulmonary hypertension. While atorvastatin reduces cholesterol, it is recognized to have many effects beyond cholesterol reduction. These include improvement of blood vessel function and reduction of fibrosis. We hypothesize that treatment with atorvastatin over 16 weeks will improve blood vessel function and Raynaud symptom in patients with early diffuse systemic sclerosis. We hope that by targeting therapy early in the disease we may delay blood vessel changes and improve Raynaud symptoms.
Detailed description
Systemic sclerosis (SSc) is a multisystem autoimmune illness characterized by vasculopathy, immune system activation and fibrosis of the skin and internal organs. SSc affects approximately 240 people per million in the US, but is a disease for which there is no FDA approved medication. Current hypothesis of pathogenesis suggest that a vascular injury with endothelial dysfunction may be an inciting event contributing to immunologic activation and fibrosis in the pathogenesis of the disease. More than 90% of individuals with SSc have vascular complications including Raynaud phenomenon, digital ulcers or gangrene and pulmonary hypertension; with microvascular abnormalities felt to contribute to Raynaud and digital ulcerations.
Statin medications are well-recognized to have pleiotropic effects which may modify all three aspects of SSc pathogenesis. Early diagnosis and treatment of microvascular endothelial dysfunction and Raynaud phenomeonan may have the greatest effect in early disease. Thus, we hypothesize that treatment with atorvastatin in a well-defined cohort of early diffuse systemic sclerosis will produce beneficial results.
Participants will be patients with early diffuse systemic sclerosis and Raynaud phenomenon who have no history of cardiovascular disease or diabetes. A total of 30 patients will be enrolled and followed for 16 weeks. Half the patients will be randomized to atorvastatin and half to placebo. Patients will be allowed to continue underlying immunosuppressive and Raynaud therapy at stable doses during the trial. Since this is a pilot study, future larger controlled trials will be necessary to clearly demonstrate drug effectiveness. Investigators are hoping that this study will give us signals to guide a future multicenter clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Drug | Active comparator | Drug: atorvastatinatorvastatin 40 mg once daily for sixteen weeks |
| Placebo control | Placebo comparator | Drug: Placeboreceive a placebo of similar appearance once daily for sixteen weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- early diffuse scleroderma (< 3 years from the first scleroderma-related symptom)
- Raynaud phenomenon
- no use of lipid-lowering medication within 60 days
Key exclusion criteria (7 listed)
- pregnancy
- renal or kidney dysfunction (creatinine < 2.0 mg/dL or creatinine clearance < 60 c/min)
- diabetes mellitus
- known cardiovascular disease or a prior history of stroke
- history of liver disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| atorvastatinAlso: LipitorAtorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy. | Drug | Active Drug |
| Placebooral drug of similar appearance to atorvastatin | Drug | Placebo control |
Primary outcome
Proportion of Patients Improving Their EndoPAT Reactive Hyperemia Index (RHI) at the End-of-study (16 Weeks)
Time frame: Change in RHI from baseline to 16 weeks expressed as the percentage of patients who improve (respond).
EndoPAT is a proprietary device that assesses digital (microvascular) endothelial function during reactive hyperemia. A probe is placed on both index fingers. After 5 minutes of baseline observation, one arm is occluded for 5 minutes, while the other is not and serves as control. Output is the reactive hyperemia index (RHI), calculated as the post-to-pre occlusion signal ratio in the occluded side, "normalized to the control side and further corrected for baseline vascular tone" per Itamar Medical. There are no units. RHI ≤ 1.67 is abnormal and indicates endothelial dysfunction.
3 secondary outcomes
Change in the Raynaud Condition Score (RCS) at 16 Weeks (End-of-study) From Baseline
Time frame: change in RCS from baseline to week 16
The Median Change in the Raynaud Phenomenon Visual Analog Scale (RP-VAS) Score at 16 Weeks (End-of-study) Compared to Baseline in the Atorvastatin and Placebo Groups.
Time frame: baseline to 16 weeks
% of Patients Who Improved Their Brachial Flow-mediation Dilation (%FMD) at 16 Weeks
Time frame: baseline to 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing atorvastatin in people with Scleroderma, run by Robyn T. Domsic, MD, MPH at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Patients Improving Their EndoPAT Reactive Hyperemia Index (RHI) at the End-of-study (16 Weeks) (time frame: Change in RHI from baseline to 16 weeks expressed as the percentage of patients who improve (respond).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2020.