Systemic Lupus ErythematosusDARENCT01781611
Dipyridamole Assessment for Flare Reduction in Systemic Lupus Erythematosus (SLE)
A study testing extended release dipyridamole 200mg/aspirin 25mg and 81mg aspirin in people with Systemic Lupus Erythematosus, run by Oklahoma Medical Research Foundation at 1 site in United States.
Trial summary
Dipyridamole, a medication extensively used in combination with aspirin for stroke prevention, is a promising new treatment for lupus. Dipyridamole has been shown to inhibit certain lymphocyte populations that are over-reactive in lupus and to delay the emergence of lupus-related pathology in mice with lupus. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- extended release dipyridamole 200mg/aspirin 25mg and 81mg aspirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Nov 2017
- Phase
- Interventional
- 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
- Patients with SLE meeting the 1997 ACR Classification Criteria
- Evidence of positive ANA or anti-dsDNA within one year of screening
- SLEDAI ≥4 or ≥1 BILAG A or B at screening, despite standard of care
Who cannot join
- Leukopenia (WBC <2.000/mm3) or lymphopenia (lymphocytes < 300/mm3)
- AST or ALT >3 times above normal cut off values
- Acute lupus nephritis defined as class II, IV or V nephritis diagnosed within 6 months or prot/creat > 1.5 gm/gm due to active lupus or in process of receiving induction therapy for nephritis
- Active CNS lupus affecting mental status
- Pregnancy or breast feeding
- Current requirement for anticoagulation
Show all 9Show fewer
- Contraindication to aspirin or dipyridamole, including history of recent or severe GI bleeding, hemoglobin <9 mg/dL, platelet count of <30,000 /mm3 or unstable platelet count
- Any other medical condition, whether or not related to lupus which, in the opinion of the investigator would render the patient inappropriate or too unstable to complete the study protocol
- Inability or unwillingness to understand and/or sign informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, 73104
About this study
Official title: Dipyridamole Assessment for Flare Reduction in SLE
Dipyridamole, a medication extensively used in combination with aspirin for stroke prevention, is a promising new treatment for lupus. Dipyridamole has been shown to inhibit certain lymphocyte populations that are over-reactive in lupus and to delay the emergence of lupus-related pathology in mice with lupus. The investigators are interested in investigating the efficacy of dipyridamole in preventing flares in patients with lupus and its impact on biomarkers of disease activity.
Read the detailed description
T cells in systemic lupus erythematosus (SLE) express an abnormal phenotype characterized by increased effector functions and deficient regulatory responses. Dipyridamole, a phosphodiesterase inhibitor extensively used in combination with low dose aspirin in secondary stroke prevention, has been proposed as a specific T cell directed treatment for SLE. Dipyridamole inhibits the calcium/calcineurin/NF-AT pathway in SLE T cells in vitro and abrogates expression of cytokines and costimulatory molecules, eventually also affecting B cell responses. Dipyridamole delays the emergence of lupus related pathology in lupus prone mice, but has not yet been studied in humans with SLE. The investigators aim to investigate the efficacy of dipyridamole in the prevention of flares in SLE patients after withdrawal of background immunosuppressive medications. The investigators will additionally evaluate the safety and tolerability of dipyridamole and its impact on quality of life measures in this population. Furthermore, the effect of dipyridamole on T and B cell biomarkers will be examined.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- extended release dipyridamole 200mg/aspirin 25mg, 81mg aspirin
- Keywords
- lupus, dipyridamole
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
extended release dipyridamole 200mg/aspirin 25mgDrug
Also called Aggrenox
one tablet twice daily for 24 weeks
81mg aspirinDrug
Also called ASA
half a tablet twice daily for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| extended release dipyridamole/aspirin | Experimental | extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks Receives: Drug: extended release dipyridamole 200mg/aspirin 25mg |
| aspirin | Active comparator | half a tablet of a 81mg aspirin twice daily for 24 weeks Receives: Drug: 81mg aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
This is a landmark measure of percentage of patients who meet response criteria. To meet the BICLA response measure a patient must, compared to baseline, have a decrease in all moderate or severe scores on the British Isles Lupus Assessment Group (BILAG) index by at least one severity grade (Severe disease (BILAG A score) must drop to at least moderate (B or better) and B must drop to at least mild (C or not present). Also, there must be no increase in any other BILAG organ scores, no increase in The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and no increase in the physician's global assessment (PGA) by more than 10% of the scale. Furthermore, there may no off protocol medication increases. Note on all scales mentioned a higher score signifies greater disease activity. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76.
Measured: 24 weeks
Secondary outcomes (2)
Systemic Lupus Erythematosus Responder Index (SRI) 4
This is a landmark analysis of percentage of patients who meet the following response criteria: Compared to baseline there must be a 4 point decrease in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), no increase in The British Isles Lupus Assessment Group (BILAG) Index score and no more of an increase in Physician's Global Assessment (PGA) than 10% of the scale. As assessed here, there must also be no off protocol increase in medications. All scales signify worsening disease when scores increase. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76.
Measured: 24 weeks
SRI Component Analyses: 4 Point Drop in SLEDAI
This is a landmark analysis of percentage of patients who, compared to baseline, have a 4 point drop in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). A 4 point decrease signifies a clinically significant decrease in disease activity as reported in many studies and as commonly used as a clinical endpoint in trials. SLEDAI could range 0-105 but is rarely greater than 20.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionMay 2017
- Study completionNov 2017
Why it stopped: Slow recruitment
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Systemic Lupus ErythematosusStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Pilot study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oklahoma Medical Research Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Katherine Thanou, MD, Principal investigator, Oklahoma Medical Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01781611
- Sponsor's protocol ID
- IRB# 12-10
- Acronym
- DARE
- Status last verified
- Nov 2020
- First submitted
- 2 Jan 2013
- Last updated
- 25 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Those who wish access to this data may contact Joan Merrill at joan-merrill@omrf.org for further information
Publications
Kyttaris VC, Zhang Z, Kampagianni O, Tsokos GC. Calcium signaling in systemic lupus erythematosus T cells: a treatment target. Arthritis Rheum. 2011 Jul;63(7):2058-66. doi: 10.1002/art.30353.
PubMed 21437870Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
PubMed 33687069
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dipyridamole Assessment for Flare Reduction in SLE
- ClinicalTrials.gov ID
- NCT01781611
- Acronym / sponsor ID
- DARE / IRB# 12-10
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- lupus, dipyridamole
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Oklahoma Medical Research FoundationUniversity, hospital or other
- Study start
- Feb 2013 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 1 Feb 2013 (estimated)
- Results
- Posted 25 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dipyridamole, a medication extensively used in combination with aspirin for stroke prevention, is a promising new treatment for lupus. Dipyridamole has been shown to inhibit certain lymphocyte populations that are over-reactive in lupus and to delay the emergence of lupus-related pathology in mice with lupus. The investigators are interested in investigating the efficacy of dipyridamole in preventing flares in patients with lupus and its impact on biomarkers of disease activity.
Detailed description
T cells in systemic lupus erythematosus (SLE) express an abnormal phenotype characterized by increased effector functions and deficient regulatory responses. Dipyridamole, a phosphodiesterase inhibitor extensively used in combination with low dose aspirin in secondary stroke prevention, has been proposed as a specific T cell directed treatment for SLE. Dipyridamole inhibits the calcium/calcineurin/NF-AT pathway in SLE T cells in vitro and abrogates expression of cytokines and costimulatory molecules, eventually also affecting B cell responses. Dipyridamole delays the emergence of lupus related pathology in lupus prone mice, but has not yet been studied in humans with SLE. The investigators aim to investigate the efficacy of dipyridamole in the prevention of flares in SLE patients after withdrawal of background immunosuppressive medications. The investigators will additionally evaluate the safety and tolerability of dipyridamole and its impact on quality of life measures in this population. Furthermore, the effect of dipyridamole on T and B cell biomarkers will be examined.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Pilot study
| Arm | Type | Receives |
|---|---|---|
| extended release dipyridamole/aspirin | Experimental | Drug: extended release dipyridamole 200mg/aspirin 25mgextended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks |
| aspirin | Active comparator | Drug: 81mg aspirinhalf a tablet of a 81mg aspirin twice daily for 24 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)
- Patients with SLE meeting the 1997 ACR Classification Criteria
- Evidence of positive ANA or anti-dsDNA within one year of screening
- SLEDAI ≥4 or ≥1 BILAG A or B at screening, despite standard of care
Key exclusion criteria (9 listed)
- Leukopenia (WBC <2.000/mm3) or lymphopenia (lymphocytes < 300/mm3)
- AST or ALT >3 times above normal cut off values
- Acute lupus nephritis defined as class II, IV or V nephritis diagnosed within 6 months or prot/creat > 1.5 gm/gm due to active lupus or in process of receiving induction therapy for nephritis
- Active CNS lupus affecting mental status
- Pregnancy or breast feeding
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 |
|---|---|---|
| extended release dipyridamole 200mg/aspirin 25mgAlso: Aggrenoxone tablet twice daily for 24 weeks | Drug | extended release dipyridamole/aspirin |
| 81mg aspirinAlso: ASAhalf a tablet twice daily for 24 weeks | Drug | aspirin |
Primary outcome
British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA)
Time frame: 24 weeks
This is a landmark measure of percentage of patients who meet response criteria. To meet the BICLA response measure a patient must, compared to baseline, have a decrease in all moderate or severe scores on the British Isles Lupus Assessment Group (BILAG) index by at least one severity grade (Severe disease (BILAG A score) must drop to at least moderate (B or better) and B must drop to at least mild (C or not present). Also, there must be no increase in any other BILAG organ scores, no increase in The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and no increase in the physician's global assessment (PGA) by more than 10% of the scale. Furthermore, there may no off protocol medication increases. Note on all scales mentioned a higher score signifies greater disease activity. Ranges on BILAG could be 0-108 but are rarely greater than 36. SLEDAI could range 0-105 but is rarely greater than 20. PGA 0-100 but rarely greater than 76.
2 secondary outcomes
Systemic Lupus Erythematosus Responder Index (SRI) 4
Time frame: 24 weeks
SRI Component Analyses: 4 Point Drop in SLEDAI
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21437870Kyttaris VC, Zhang Z, Kampagianni O, Tsokos GC. Calcium signaling in systemic lupus erythematosus T cells: a treatment target. Arthritis Rheum. 2011 Jul;63(7):2058-66. doi: 10.1002/art.30353.
- Derived from this study: PubMed 33687069Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
- Individual participant dataSharing planned: Yes. Those who wish access to this data may contact Joan Merrill at joan-merrill@omrf.org for further information
Related trials for Systemic Lupus Erythematosus
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
RecruitingPhase 4
Dapagliflozin in Active Lupus Nephritis
Lupus Nephritis (LN)
RecruitingObservational study
Electroencephalogram Recording in Patients With Systemic Lupus Erythematosus
Systemic Lupus Erythematosus
RecruitingObservational study
Deciphering the Genetic Architecture of Autoimmune Diseases
Autoimmune Diseases
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
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.
Katherine Thanou, MD principal investigator
Oklahoma Medical Research Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing extended release dipyridamole 200mg/aspirin 25mg and 81mg aspirin in people with Systemic Lupus Erythematosus, run by Oklahoma Medical Research Foundation 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 9 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: stopped early, as of the sponsor's last update on 25 Nov 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Nov 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?
British Isles Lupus Assessment Group Index-based Combined Lupus Assessment (BICLA) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01781611, which also lists 2 linked publications.
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 25 Nov 2020.