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Dipyridamole Assessment for Flare Reduction in Systemic Lupus Erythematosus (SLE) (DARE)

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ClinicalTrials.gov Identifier: NCT01781611
Recruitment Status : Terminated (Slow recruitment)
First Posted : February 1, 2013
Results First Posted : November 25, 2020
Last Update Posted : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Oklahoma Medical Research Foundation

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Drug: extended release dipyridamole 200mg/aspirin 25mg Drug: 81mg aspirin Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Pilot study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dipyridamole Assessment for Flare Reduction in SLE
Actual Study Start Date : February 2013
Actual Primary Completion Date : May 2017
Actual Study Completion Date : November 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: extended release dipyridamole/aspirin
extended release dipyridamole 200mg/aspirin 25mg twice daily for 24 weeks
Drug: extended release dipyridamole 200mg/aspirin 25mg
one tablet twice daily for 24 weeks
Other Name: Aggrenox

Active Comparator: aspirin
half a tablet of a 81mg aspirin twice daily for 24 weeks
Drug: 81mg aspirin
half a tablet twice daily for 24 weeks
Other Name: ASA




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Systemic Lupus Erythematosus Responder Index (SRI) 4 [ Time Frame: 24 weeks ]
    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.

  2. SRI Component Analyses: 4 Point Drop in SLEDAI [ Time Frame: 24 weeks ]
    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.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01781611


Locations
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United States, Oklahoma
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States, 73104
Sponsors and Collaborators
Oklahoma Medical Research Foundation
Investigators
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Principal Investigator: Katherine Thanou, MD Oklahoma Medical Research Foundation
  Study Documents (Full-Text)

Documents provided by Oklahoma Medical Research Foundation:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Oklahoma Medical Research Foundation
ClinicalTrials.gov Identifier: NCT01781611    
Other Study ID Numbers: IRB# 12-10
First Posted: February 1, 2013    Key Record Dates
Results First Posted: November 25, 2020
Last Update Posted: November 25, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Those who wish access to this data may contact Joan Merrill at joan-merrill@omrf.org for further information
Supporting Materials: Study Protocol
Time Frame: The data will be available on or before June 1 2021
Access Criteria: For de-identified data only: Please submit a two page request describing the research you wish to do and the investigators credentials and current employment. This will be reviewed by our cohort advisory board and IRB prior to release.
Keywords provided by Oklahoma Medical Research Foundation:
lupus
dipyridamole
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Aspirin
Dipyridamole
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Phosphodiesterase Inhibitors
Vasodilator Agents