Sensory Testing for Sickle Cell Disease

Overseen By Nirmish Shah, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Disqualifiers: Pregnancy, Stroke, Infection, Neuropathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

70 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants who are on chronic pain medications like NSAIDs, acetaminophen, or opioids must be on a stable dose for at least 4 weeks before joining. So, you won't have to stop taking them, but you need to be on a consistent dose.

What data supports the effectiveness of the treatment Quantitative Sensory Testing (QST) for sickle cell disease?

Quantitative Sensory Testing (QST) is used to understand pain and sensory processing in sickle cell disease, and it has shown that thermal testing may be sensitive to effective therapies like hydroxycarbamide, which can reduce pain sensitivity over time. This suggests QST can be a useful tool in evaluating pain management strategies for sickle cell disease. ^{1 2 3 4 5}

Is Quantitative Sensory Testing (QST) safe for humans?

Quantitative Sensory Testing (QST) is generally considered safe and well-tolerated in humans, including those with sickle cell disease. Studies have shown that it is feasible to use and does not cause significant adverse effects. ^{1 2 3 4 6}

How is the treatment Quantitative Sensory Testing (QST) different from other treatments for sickle cell disease?

Quantitative Sensory Testing (QST) is unique because it is a noninvasive method used to assess sensory nerve function and pain processing, rather than directly treating sickle cell disease. It helps to understand the types of pain and altered pain processing in patients, which can guide the management of chronic pain in sickle cell disease. ^{1 2 3 4 7}

What is the purpose of this trial?

Sickle cell disease is a painful inherited disorder that affects approximately 100,000 people in the United States, and more than half of these individuals develop chronic or persistent pain that is often severe and disabling. The factors that predict whether an individual with sickle cell disease will develop severe, disabling pain are unclear. The goal of this project is to identify the factors that predict severe pain outcomes in individuals living with sickle cell disease in order to improve pain management strategies and guide future studies of non-opioid therapies for treatment of their pain. Participants who agree to enroll in this study will be asked to participate in a virtual and then an in-person study visit for their full initial study assessment. They will answer survey questions during the virtual visit, and will be asked to complete several types of standard testing to understand how their body handles pain during the in-person visit. After completing the virtual and in-person sessions, participants will receive text or electronic medical record messages with brief survey (will take less than 8 minutes to complete) on their pain experiences every three months until the study is completed (or up to 48 months for people who are enrolled at the beginning of the study).

Research Team

Martha Kenney, MD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for individuals aged 15-40 with sickle cell disease who've had a pain episode treated with opioids in the past year. They must be on stable pain medication doses for 4 weeks and provide consent (parental if under 18).

Inclusion Criteria

I have had a sickle cell pain crisis treated with opioids in the last year.

I am between 15 and 40 years old and can provide consent or have parental consent if under 18.

I have been diagnosed with sickle cell disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Assessment

Participants complete a virtual visit with survey questions followed by an in-person visit for standard testing to understand pain handling

1-2 weeks

1 virtual visit, 1 in-person visit

Longitudinal Monitoring

Participants receive brief surveys on pain experiences every three months

Up to 48 months

Electronic surveys every 3 months

Follow-up

Participants are monitored for changes in pain severity, interference, healthcare utilization, psychological distress, and physical function

4 weeks

Treatment Details

Interventions

• Quantitative sensory testing

Trial Overview The study aims to identify predictors of severe pain in sickle cell patients to improve management strategies. It involves virtual surveys and in-person quantitative sensory testing, followed by regular brief surveys over up to four years.

Participant Groups

Group I: Individuals living with sickle cell disease Experimental Treatment 1 Intervention

Participants living with sickle cell disease will undergo standardized testing called quantitative sensory testing. Quantitative sensory testing measures changes in sensitivity to different type of sensations that include temperature, touch or pressure.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

Chronic pain affects over 50% of adults with sickle cell disease (SCD), and this scoping review analyzed 27 studies to understand the methodologies of quantitative sensory testing used to assess pain and sensory processing in this population.

The review found significant variability in testing methods across studies, with many reporting sensory abnormalities, particularly in thermal pain thresholds and temporal summation, highlighting the need for standardized protocols to better understand pain mechanisms in SCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered pain processing and sensitization in sickle cell disease: a scoping review of quantitative sensory testing findings. Kenney, MO., Knisely, MR., McGill, LS., et al.[2023]

In a study involving 57 sickle cell disease (SCD) patients and 60 control subjects aged 8-20, no significant differences in thermal pain thresholds were found between the two groups, indicating that QST may not effectively differentiate pain sensitivity in SCD compared to controls.

However, for new users of hydroxycarbamide, a treatment for SCD, there was a notable decrease in thermal sensitivity over 6 months, suggesting that QST could be a useful tool for monitoring the effectiveness of therapies aimed at preventing vaso-occlusive pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative sensory testing in children with sickle cell disease: additional insights and future possibilities. Miller, RE., Brown, DS., Keith, SW., et al.[2020]

The quantitative sensory testing (QST) protocol was found to be safe for adults with sickle cell disease (SCD) and did not trigger a pain crisis, indicating its potential utility for assessing pain mechanisms in this population.

The study revealed evidence of central and peripheral sensitization in many participants, suggesting a neuropathic component to SCD pain, with 40% of subjects showing signs of neuropathic pain based on self-report tools.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Utility of Quantitative Sensory Testing among Adults with Sickle Cell Disease: Indicators of Neuropathic Pain? Ezenwa, MO., Molokie, RE., Wang, ZJ., et al.[2022]

Quantitative sensory testing (QST) is feasible and well-tolerated in pediatric patients with sickle cell disease (SCD) following a vaso-occlusive episode (VOE), with 62.5% of approached patients completing the test.

There were no significant differences in pain intensity after QST following a VOE compared to steady-state measurements, suggesting that VOE may not immediately alter pain sensitivity as measured by QST.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative sensory testing is feasible and is well-tolerated in patients with sickle cell disease following a vaso-occlusive episode. Bakshi, N., Lukombo, I., Belfer, I., et al.[2022]

The study developed a new scoring system called PR-Lasso, which effectively distinguishes between sensitized and normal sensation pain phenotypes in African American adults with sickle cell disease, using sensory pain quality descriptors.

The PR-Lasso score showed strong correlations with existing pain assessment tools and outperformed them, particularly the S-LANSS, indicating its potential as a more accurate measure for assessing pain in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A QST-based Pain Phenotype in Adults With Sickle Cell Disease: Sensitivity and Specificity of Quality Descriptors. Dyal, BW., Ezenwa, MO., Yoon, SL., et al.[2022]

Quantitative sensory testing (QST) shows potential in identifying sensory abnormalities in conditions like diabetic neuropathy, but there is no strong evidence from well-powered studies to confirm its effectiveness for specific disorders.

Due to variability between different QST systems and the lack of consensus on reproducibility, results from one system cannot be directly compared to another, highlighting the need for standardized methodologies in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Shy, ME., Frohman, EM., So, YT., et al.[2022]

Quantitative sensory testing (QST) is a reliable and well-accepted method for assessing sensory function in children aged 6-17, with good reproducibility across sessions, making it suitable for clinical use.

The study established normal sensory detection thresholds for cold, warm, cold pain, heat pain, and vibration in both hands and feet, which can help monitor sensory abnormalities in children with neurological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative assessment of cutaneous thermal and vibration sensation and thermal pain detection thresholds in healthy children and adolescents. Meier, PM., Berde, CB., DiCanzio, J., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Altered pain processing and sensitization in sickle cell disease: a scoping review of quantitative sensory testing findings. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Quantitative sensory testing in children with sickle cell disease: additional insights and future possibilities. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Safety and Utility of Quantitative Sensory Testing among Adults with Sickle Cell Disease: Indicators of Neuropathic Pain? [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Quantitative sensory testing is feasible and is well-tolerated in patients with sickle cell disease following a vaso-occlusive episode. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

A QST-based Pain Phenotype in Adults With Sickle Cell Disease: Sensitivity and Specificity of Quality Descriptors. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Quantitative assessment of cutaneous thermal and vibration sensation and thermal pain detection thresholds in healthy children and adolescents. [2022]