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

November 3, 2020 updated by: Oklahoma Medical Research Foundation

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

18

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma Medical Research Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • ASA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
24 weeks
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.
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oklahoma Medical Research Foundation

Investigators

  • Principal Investigator: Katherine Thanou, MD, Oklahoma Medical Research Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2013

Primary Completion (Actual)

May 1, 2017

Study Completion (Actual)

November 1, 2017

Study Registration Dates

First Submitted

January 2, 2013

First Submitted That Met QC Criteria

January 30, 2013

First Posted (Estimate)

February 1, 2013

Study Record Updates

Last Update Posted (Actual)

November 25, 2020

Last Update Submitted That Met QC Criteria

November 3, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB# 12-10

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Those who wish access to this data may contact Joan Merrill at joan-merrill@omrf.org for further information

IPD Sharing Time Frame

The data will be available on or before June 1 2021

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • Study Protocol

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Systemic Lupus Erythematosus

Clinical Trials on extended release dipyridamole 200mg/aspirin 25mg

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Serbia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe