Adenosine 2A Agonist Lexiscan in Children and Adults With Sickle Cell Disease

Sickle cell disease (SCD) is an inherited blood disorder that causes the red blood cells to change their shape from a round shape to a half-moon/crescent or sickled shape. People who have SCD have a different type of protein that carries oxygen in their blood (hemoglobin) then people without SCD. This different type of hemoglobin makes the red blood cells change into a crescent shape under certain conditions. Sickle-shaped cells are a problem because they often get stuck in blood vessels blocking the flow of blood, and cause inflammation and injury to the important areas in the body. Lexiscan is drug that may prevent this inflammation and injury caused by the sickle shaped cells. This drug is approved by the FDA to be used as a fast infusion during a heart stress test in people who are unable to exercise enough to put stress on their heart by making it beat faster. Lexiscan has never been studied in patients with SCD and has never been given as a long infusion.

* In this research study we are looking for the highest dose of Lexiscan that can be given safely to patients with SCD. There are 4 stages to this study. Each stage will look for the highest dose that can be given safely in the following situations: Stage 1: Lexiscan will be given through a 12 hours infusion to adults with SCD who are not having a pain crisis. Stage 2: Lexiscan will be given through a 24 hour infusion to adults with SCD who are not having a pain crisis. Stage 2b: Lexiscan will be given through a 48 hour infusion to adults with SCD who are not having a pain crisis. Stage 3: Lexiscan will be given through a 24 hour infusion to adults with SCD who are having a pain crisis. Stage 4: Lexiscan will be given through a 24 hour infusion to children with SCD who are having a pain crisis. Stages 1-3 are now complete and closed to accrual. The study is now open to children ages 10-17 with SCD pain crisis (stage 4) only.
* When participants sign the consent form, they will be told what stage they will join.
* Participants in Stages 1, 2, and 2b will be given an infusion of the study drug at the time when they do not have a pain crisis. The infusion for Stage 1 participants will be 12 hours long, followed by a 6-hour observation period. The infusion for Stage 2 will be 24 hours long, followed by a 6-hour observation period. The infusion for Stage 2b will be 48 hours long, followed by a 6-hour observation period.
* Participants in Stages 3 and 4 will be given one infusion of the study drug when they are admitted to the hospital for a pain crisis. The infusion will be 24 hours long, followed by a 6-hour observation period. During the infusion, they will receive standard treatment for their pain crisis.
* Before the infusion the following procedures will be performed: Pulmonary function test (optional, Stage 1 only), blood test and vital signs.
* During the infusion the following procedures will be performed: heart rate and amount of oxygen in the blood will be monitored continuously, blood tests and blood pressure.
* During the observation period immediately following the infusion the following procedures will be performed: heart rate and amount of oxygen in the blood will be monitored continuously, blood tests, blood pressure and Pulmonary Function test (optional, Stage 1 only).

Eligibility Criteria:
Inclusion Criteria Stage I/II/IIb: (COMPLETE AND CLOSED TO ACCRUAL)

* Participants must have sickle cell anemia confirmed by hemoglobin analysis
* Participants must report that their pain is at baseline. Additionally, they cannot report an increase in dose or frequency of opioid use in the last 2 weeks prior to drug administration
* Age 21-70 years
* Participants must have the laboratory indices as outlined in the protocol
* Participants must have reliable IV access as determined by the investigator
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study.

Inclusion Criteria Stage III: (COMPLETE AND CLOSED TO ACCRUAL)

* Participants must have sickle cell anemia confirmed by hemoglobin analysis
* Participant is admitted to the hospital for a pain episode
* Age 21-70 years
* Participants must have the laboratory indices as outlined in the protocol
* Participants must have reliable IV access as determined by the investigator
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Inclusion Criteria Stage IV: (open, still accruing volunteers)

* Participants must have sickle cell disease confirmed by hemoglobin analysis
* Participant is admitted to the hospital for a pain episode
* Ages of assent (10 to 17 years at DFCI, but different depending on institution)
* Participants must have the laboratory indices as outlined in the protocol
* Participants must have reliable IV access as determined by the investigator
* Participants and parents must have the ability to understand and the willingness to sign a written informed consent and assent document
* Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria Stage I/II/IIb: (COMPLETE AND CLOSED TO ACCRUAL)

* Participants with a current physician diagnosis of asthma (within last 12 months), require continuous supplemental oxygen, or predicted or current use of some asthma medications.
* Participants with second- or third-degree AV block or sinus node dysfunction
* Have a history of bleeding diathesis
* Have a history of clinically overt stroke
* Have a history of severe hypertension not adequately controlled with anti-hypertensive medications
* Participants who are receiving chronic anti-coagulation or anti-platelet therapy
* Participants with a history of metastatic cancer
* Participants who have had a hospitalization or emergency room visit for any reason in the past 2 weeks
* Participants may not be receiving any other study agents or have received a study agent in the past 30 days
* Uncontrolled intercurrent illness
* Pregnant or breastfeeding women
* Participants with HIV
* Participants who have previously enrolled and received the investigational agent as part of this study
* Participants who are taking medications that may interact with the investigational agent

Exclusion Criteria Stage III: (COMPLETE AND CLOSED TO ACCRUAL)

* Participants with a current physician diagnosis of asthma (within last 12 months), require continuous supplemental oxygen, or predicted or current use of some asthma medications.
* Participants with second- or third-degree AV block or sinus node dysfunction
* Have a history of bleeding diathesis
* Have a history of clinically overt stroke
* Have a history of severe hypertension not adequately controlled with anti-hypertensive medications
* Participants who are receiving chronic anti-coagulation or anti-platelet therapy
* Participants with a history of metastatic cancer
* Participants may not be receiving any other study agents or have received a study agent in the past 30 days

Exclusion Criteria Stage IV: (open, still accruing volunteers)

* Participants with a current physician diagnosis of asthma (within last 12 months), require continuous supplemental oxygen, or predicted or current use of some asthma medications.
* Participants with second- or third-degree AV block or sinus node dysfunction
* Have a history of bleeding diathesis
* Have a history of clinically overt stroke
* Have a history of hypertension not adequately controlled with anti-hypertensive medications
* Participants who are receiving chronic anti-coagulation or anti-platelet therapy
* Participants with a history of metastatic cancer
* Participants may not be receiving any other study agents or have received a study agent in the past 30 days
* Participants with HIV
* Participants who have previously enrolled and received the investigational agent as part of this study
* Participants who are taking medications that may interact with the investigational agent