Clinical Trials Logo

Clinical Trial Summary

Background:

- Pain is the most common symptom of sickle cell disease. Episodes of severe sickle cell pain are known as "crises." High rates of pain crises are associated with a higher risk of early death. Some people with sickle cell disease have many severe pain crises while others experience fewer crises. This difference in pain crisis may be caused by sensitivity to pain. People with high sensitivity to pain may have more pain crises. Many factors, including a person's genetic makeup, determine sensitivity to pain. Comparing genetic information from people with sickle cell disease and healthy volunteers may provide more information on pain and sickle cell disease.

Objectives:

- To study genetics and pain sensitivity in sickle cell disease.

Eligibility:

- African or African American individuals at least 18 years of age with sickle cell disease.

- Healthy African or African American volunteers at least 18 years of age.

Design:

- Participants will be screened with a medical history and physical exam. They will also provide blood and urine samples.

- Participants will have the following tests:

- Quantitative sensory testing to measure sensitivity to pressure, heat, cold, and mechanical pain.

- EndoPat test to measure blood vessel function and reaction.

- Questionnaires about mood, evidence of depression, pain, quality of sleep, and sleep disturbances.

- Measures of daily pain, whether or not related to sickle cell disease.

- After the first visit, those in the study will have monthly study visits for 6 months. The above tests will be repeated at these visits.


Clinical Trial Description

Sickle cell disease (SCD) is the most common genetic disease in the United States inherited as an autosomal recessive disorder, where approximately 70,000 individuals have sickle cell disease. Acute painful vaso-occlusive crisis (VOCs) is one of the common complications of SCD that influences overall survival (Platt, Thorington et al. 1991). Pain, is also the most common cause of SCD morbidity, which has a negative impact on quality of life of these individuals and their families. There is significant inter-individual variation in the frequency and course of severe VOCs that result in hospital based treatment, the reasons for which have not been clearly elucidated. Vaso-occlusion of irreversibly sickle red cells within the microcirculation is believed to be the proximate cause of painful VOCs, however it is likely that other non-SCD related factors affecting pain perception and sensitivity to pain will also contribute to individuals susceptibility to pain and therefore contribute to the observed inter-individual variability in the course of VOC. Early identification of individuals who are at high risk for developing severe pain related morbidity and chronic pain syndromes is crucial since early multimodal interventions might have the potential to minimize both the morbidity and mortality associated with VOCs.

<TAB>

Patients with SCD are hypothesized to have lower nitric oxide (NO) bioavailability due to NO scavenging by cell free hemoglobin released into plasma during red cell hemolysis. NO deficiency has been identified as a key factor in development vascular dysfunction in SCD. NO has also recently been identified as a key mediator in processing nociceptive signals and modulation of pain in non-SCD models. Thus, low NO is associated with lower pain perception (Meller, Dykstra et al. 1992; Tegeder, Costigan et al. 2006). GTP cyclohydrolase (GCH1) is the rate-limiting enzyme for synthesis of an essential cofactor for both NO production and metabolism of aromatic amino acids, namely tetrahydrobiopterin (BH4). Therefore it is hypothesized that genetic variants in the GCH1 gene will affect BH4 levels and which will have a secondary impact on vascular dysfunction and sensitivity to pain in SCD.

The primary goal of this protocol is to establish patterns of sensitivity to experimental pain among subjects with SCD compared to healthy African American controls. In addition, an exploratory analysis will determine if increased sensitivity to experimental pain correlates with the frequency and intensity of clinical pain in those with SCD. Once an expected pattern of experimental pain phenotypes are established for a cohort with SCD, we will then further explore the role of GCH1 genetic variants in experimental pain perception and vascular function. If successful, a longer term secondary objective is to establish a sufficiently large patient cohort with experimental pain phenotypes for future exploratory genetic studies to investigate the role of other loci that might influence sensitivity to experimental pain and vascular function in SCD. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT01441141
Study type Observational
Source National Institutes of Health Clinical Center (CC)
Contact
Status Completed
Phase
Start date September 7, 2011

See also
  Status Clinical Trial Phase
Recruiting NCT03273114 - Cognitive Functional Therapy (CFT) Compared With Core Training Exercise and Manual Therapy (CORE-MT) in Patients With Chronic Low Back Pain N/A
Recruiting NCT03286543 - Electrical Stimulation for the Treatment of Pain Following Total Knee Arthroplasty Using the SPRINT Beta System N/A
Completed NCT02913027 - Can We Improve the Comfort of Pelvic Exams? N/A
Terminated NCT02181387 - Acetaminophen Use in Labor - Does Use of Acetaminophen Reduce Neuraxial Analgesic Drug Requirement During Labor? Phase 4
Completed NCT01077414 - Phenomenological Study of Psycho-Socio-Spiritual Healing in the Context of Chronic or Life-Threatening Illness
Completed NCT01198197 - PET Brain and Whole Body Distribution Studies for Nociceptin/Orphanin FQ Peptide (NOP) Receptor Using [11C]NOP-1A Early Phase 1
Enrolling by invitation NCT03272139 - Interscalene Block Versus Superior Trunk Block Phase 4
Completed NCT03459872 - Acupuncture Outcomes Based Rehabilitation N/A
Recruiting NCT03256487 - Intravenous Buprenorphine Versus Morphine for Severe Pain in the Emergency Department Phase 2
Recruiting NCT03170557 - Randomized Comparative Trial for Persistent Pain in Spinal Cord Injury: Acupuncture vs Aspecific Needle Skin Stimulation N/A
Completed NCT02533908 - Combination of Nitrous Oxide 70% With Fentanyl Intranasal for Procedural Analgosedation in Children Phase 3
Recruiting NCT02829736 - ThOracoscopic Wedge Resection Treated With Chest Tube Removal Intraoperatively N/A
Recruiting NCT02943772 - Does Local Cooling of Testis in Patients With Epididymitis Relieve Pain and Reduce Quantity of Analgetics Intake? N/A
Recruiting NCT02911168 - Comparison of US-Guided Paravertebral and Proximal Intercostal Nerve Blocks N/A
Active, not recruiting NCT02917603 - Shared Decision Making to Improve Palliative Care in the Nursing Home N/A
Completed NCT02839889 - Tolerability, Safety, and Feasibility of Naloxegol in Patients With Cancer and OIC (Opioid Induced Constipation) Phase 4
Not yet recruiting NCT02840942 - Robots to Reduce Pain During IV Placement N/A
Not yet recruiting NCT02851940 - Pain and Bleeding Following Hypertonic Saline Sclerotherapy Compared to Brand Ligation for Symptomatic Hemorrhoids N/A
Completed NCT02916927 - Intravenous Sub-dissociative Dose Ketamine Injection Versus Infusion for Analgesia in the Emergency Department Phase 4
Not yet recruiting NCT02834481 - Assessment of Pain Monitoring With ANI/NIPE Monitor Program in Pediatric Cardiac Surgery Postoperative. Phase 4