Genetics and Pain Severity in Sickle Cell Disease

NCT01441141 | Completed

• 2 other identifiers: 11025211-H-0252
• Study Type: observational
• Target: 67
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Genotype; Pain; Genetic Variation; Quantitative Sensory Testing (QST); GCH1

Keywords

GCH1; Pain Sensitivity; Quantitative Sensory Testing (QST); Genetic Variation; Sickle Cell Anemia

Outcome Measures

Primary Outcomes (1)

• To determine if thresholds for pain perception are lower in SCD than in non-SCD controls.

  lower pain threshold in SCD than in non-SCD controls

  Ongoing

Secondary Outcomes (2)

• To determine if SCD subjects with higher GCH1 activity have 1) lower pain perception thresholds, 2) a higher prevalence of pain/VOC, 3) altered vascular reactivity and 4) more frequent pain co-morbidities) compared to subjects who lack this.

  Ongoing

• To determine if variants in the GCH1 gene alter thresholds for pain perception in sickle cell disease.

  Ongoing

Study Arms (2)

Arm 1

Subjects with SCD

Arm 2

Subjects without SCD

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

primary clinical

You may qualify if:

• Diagnosis of sickle cell disease (documentation of SS, SC, S beta + thalassemia, S beta + thalassemia by electrophoresis is required).
• If taking chronic analgesics (NSAID, acetaminophen) or opioids, study subjects should be on a stable dose for 4 weeks prior to recruitment.
• Hemoglobin AA genotype by HPLC or hemoglobin electrophoresis.
• General good health defined as the absence of untreated major medical conditions (e.g. uncontrolled systemic hypertension, etc.).

You may not qualify if:

• History of severe vaso-occlusive pain crisis resulting in either evaluation in an emergency department or admission to a hospital during the two weeks prior to study enrollment.
• Acute pain at the time of enrollment defined as spontaneous recent onset pain with a self rated score of 6 or higher on a scale of 0-10. (This is acute pain not the pain that subjects function at on a daily basis.)
• Acute pain or injury at enrollment or a recent history of chronic pain (daily pain reported for at least 6 months) in the past 3 years.
• Major medical/psychiatric illness known to cause pain.
• Sickle cell trait.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Ataga KI, Moore CG, Jones S, Olajide O, Strayhorn D, Hinderliter A, Orringer EP. Pulmonary hypertension in patients with sickle cell disease: a longitudinal study. Br J Haematol. 2006 Jul;134(1):109-15. doi: 10.1111/j.1365-2141.2006.06110.x.

  PMID: 16803576 BACKGROUND

• Bookman EB, Langehorne AA, Eckfeldt JH, Glass KC, Jarvik GP, Klag M, Koski G, Motulsky A, Wilfond B, Manolio TA, Fabsitz RR, Luepker RV; NHLBI Working Group. Reporting genetic results in research studies: summary and recommendations of an NHLBI working group. Am J Med Genet A. 2006 May 15;140(10):1033-40. doi: 10.1002/ajmg.a.31195.

  PMID: 16575896 BACKGROUND

• Campbell CM, Kronfli T, Buenaver LF, Smith MT, Berna C, Haythornthwaite JA, Edwards RR. Situational versus dispositional measurement of catastrophizing: associations with pain responses in multiple samples. J Pain. 2010 May;11(5):443-453.e2. doi: 10.1016/j.jpain.2009.08.009.

  PMID: 20439057 BACKGROUND

• Darbari DS, Vaughan KJ, Roskom K, Seamon C, Diaw L, Quinn M, Conrey A, Schechter AN, Haythornthwaite JA, Waclawiw MA, Wallen GR, Belfer I, Taylor JG 6th. Central sensitization associated with low fetal hemoglobin levels in adults with sickle cell anemia. Scand J Pain. 2017 Oct;17:279-286. doi: 10.1016/j.sjpain.2017.08.001. Epub 2017 Sep 30.

  PMID: 28969994 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pain; Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Swee Lay Thein, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2011
• First Posted: September 27, 2011
• Study Start: June 17, 2012
• Primary Completion: May 31, 2016
• Study Completion: December 9, 2020
• Last Updated: December 10, 2020

Record last verified: 2020-12

Locations

US (1)