Clinical trial NCT06725550: Integrative Medicine in Pain Management in Sickle Cell Disease
Official title: Integrative Medicine in Pain Management in Sickle Cell Disease: Assessing the Clinical Efficacy and Neurobiological Impact With Acupuncture
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Sickle Cell Disease
Pain
Acupuncture
Quantitative Sensory Testing
Magnetic Resonance Imaging
Circulating Biomarkers
Electroencephalography
Functional Near-infrared Spectroscopy
Keywords: Sickle cell disease
Pain
Acupuncture
Quantitative Sensory Testing
Magnetic Resonance Imaging
Circulating Biomarkers
Electroencephalography
Functional Near-infrared Spectroscopy
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2024-12-10
Enrollment: 120
Sex: ALL
Minimum age (years): 14
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The proposed research is to determine the clinical efficacy and neurobiological mechanisms of acupuncture analgesia in patients with sickle cell disease.

Detailed description: This study will help the investigators to learn whether acupuncture, which is a non-opioid alternative pain management approach, can help to manage pain in patients with sickle cell disease and the underlying mechanisms. Acupuncture involves inserting very fine needles through the skin at specific points on the body to different depths. Acupuncture may help relieve pain and it is used for a wide range of pain conditions. Participation in this study will include 14 study visits over around 6-8 weeks and 12 months follow-up visits. This is a randomized study, which means subjects are randomly assigned to one of two groups. During the study visits: 1) Subjects will be randomized to 10 sessions with either traditional acupuncture (very fine acupuncture needles will be inserted into the skin) or laser acupuncture without needles (a laser acupuncture device will be used and there will be no physical contact between the device and subject's skin) and each session will last for 30 minutes, 2) Subjects will answer questions about their personal and health related information for assessing health condition during the in-person and follow-up study visits, 3) Investigators will perform quantitative sensory testing (QST) before and after the acupuncture sessions on the surface of selected testing areas in subjects to assess the somatosensory functionality, 4) Investigators will record brain signals before and after acupuncture sessions using magnetic resonance imaging (MRI)-an imaging tool to analyze brain structural and functional features and metabolites profile, functional near-infrared spectroscopy (fNIRS)-an imaging tool to examine the brain hemodynamic activity, and electroencephalography (EEG) -an imaging tool used to detect the brain electrical activity, 5) Subjects will receive evoked pain stimuli on the left gastrocnemius muscle during MRI, fNIRS and EEG, 6) Female subjects will take a urine pregnancy test during the screening visit as well as before each behavioral and MRI visit, 7) Investigators will collect an inner eyelid image collection for examining the hemoglobin level and 8) subjects will have two blood draws before and after the entire acupuncture sessions for regular blood examination and circulating biomarkers' analyses. Some details regarding the interventions are purposefully omitted at this time to preserve scientific integrity. They will be included after the trial is complete.

Eligibility criteria: Inclusion Criteria:

* Any gender
* 14-17 (Adolescents) and 18-80 (Adults) years old
* Right-handed
* Either outpatient or inpatient or status changing between each other
* Have been diagnosed with SCD (includes but not limited to SS, SC or other type) and experiencing chronic pain in the past 6 months or vaso-occlusive crisis (VOC) in the past 12 months.
* Analgesic therapy prescribed by primary hematologists (or physicians for emergency or primary care) including pain-relieving medications (e.g. Morphine, coderin, Fentanyl, Oxycodone), Hydroxyurea (e.g. Droxia, Hydrea, Siklos), L-glutamine oral powder (Endari), Crizanlizumab (Adakveo), Voxelotor (Oxbryta), and/or other palliative treatment allowed, not required.
* Willing to limit the current and the introduction of any new medications or treatment modalities for control of pain symptoms during the study visits.
* Able to travel to the study site for participating scheduled visits (questionnaires, QST, EEG and MRI) and receive acupuncture treatments up to two times weekly for 5 weeks as scheduled.
* We will recruit without regard to ethnicity, however, due to the genetic nature of SCD, subjects will primarily be African-American or of African descent, although there are individuals with SCD who come from Hispanic, southern European, Middle Eastern, or Asian Indian backgrounds. The ethnic distribution in our prior studies is 95% Black/African American with 5% Hispanic or Latino (of any race). As these are minority groups many individuals may be from lower income situations.
* Fluent in English and capable of giving written informed consent.

Exclusion Criteria:

* Subjects with Covid-19 suspicion or confirmation
* Recent/ongoing alternative pain management with acupuncture or acupuncture-related techniques within the last 6-months.
* Presence of a known coagulation abnormality: Thrombocytopenia (mild thrombocytopenia with a platelets range of 51,000-100,000/ul will be further evaluated for inclusion consideration), or bleeding diathesis that may preclude the safe use of acupuncture.
* Presence of a concurrent autoimmune or inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc. that causes pain or any other chronic pain condition with pain greater than sickle pain.
* Diseases/conditions history includes but not limited to:

  * head injury with substantial loss of consciousness
  * peripheral neuropathy of known cause that interferes with activities of daily living
  * known non-SCD related Severe psychiatric illnesses (e.g. current schizophrenia, major depression with suicidal ideation).
  * significant visual, motor, or auditory impairment that would interfere with ability to perform study visits-related activities
* Medication:

Recent (30 days) initiation or dose adjustment of stimulant medications, such as those used to treat ADD/ADHD (e.g., amphetamine/dextroamphetamine \[Adderall®\], methylphenidate, dextroamphetamine), or the fatigue associated with sleep apnea or shift work (e.g., modafinil).

* Contraindications to MRI scans includes but are not limited to: surgical clips, surgical staples, metal implants, cardiac rhythmic disorders, seizure disorders, and certain metallic dental material will not be scheduled for MRI visits.
* History vascular surgery in lower limbs or current lower limb vascular dysfunction will not receive conditioned pressure pain stimuli in the lower limb.
* Subjects with Worker's Compensation, Workman's Compensation, civil litigation or disability claims pertinent to the subject's sickle disease; current involvement in out-of-court settlements for claims pertinent to the subject's sickle disease; or currently receiving monetary compensation as a result of any of the above.
* Participation of other studies: Concurrent participation in other therapeutic trials with overlapping research purposes.
* Pregnant or nursing.

Primary outcomes:
measure: Functional brain connectivity characteristics
timeFrame: changes brain connectivity features from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Somatosensory function
timeFrame: changes of quantitative sensory testing scores from baseline to post-treatment time point (approximately 5 weeks interval)
Secondary outcomes:
measure: Brain metabolites characteristics
timeFrame: changes of brain metabolites levels from baseline to post-treatment time point (approximately 5 weeks interval)
measure: painDETECT Questionnaire
timeFrame: changes of painDETECT scores from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Brief Pain Inventory (BPI) Questionnaire
timeFrame: changes of BPI scores from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Nociplastic Pain Questionnaire
timeFrame: changes of nociplastic scores from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Hospital Anxiety and Depression Scale (HADS) Questionnaire
timeFrame: changes of HADS scores from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Psychological Screening Questionnaires (PHQ-9)
timeFrame: changes of PHQ-9 scores from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Questionnaire
timeFrame: changes of PROMIS-29 scores from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Multidimensional Fatigue Inventory (MFI) Questionnaire
timeFrame: changes of MFI scores from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Pittsburgh Sleep Quality Index (PSQI) Questionnaire
timeFrame: changes of PSQI scores from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Adult Sickle Cell Quality Measure (ASCQ-ME) Questionnaire
timeFrame: changes of pain-related quality of life scores from baseline to post-treatment time point (approximately 5 weeks interval), as well as monthly follow-up visits till the 12th month of last in-person visit.
measure: Pediatric Quality of Life Inventory (PedsQL, both pediatric and adult versions) Questionnaire
timeFrame: changes of pain-related quality of life scores from baseline to post-treatment time point (approximately 5 weeks interval), as well as monthly follow-up visits till the 12th month of last in-person visit.
Other outcomes:
measure: Circulating biomarkers' profile and levels
timeFrame: changes of circulating biomarkers levels from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Blood hemoglobin level
timeFrame: changes of blood hemoglobin level from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Brain hemodynamic activity
timeFrame: changes of brain hemodynamic activity from baseline to post-treatment time point (approximately 5 weeks interval)
measure: Brain structural characteristics
timeFrame: changes of brain structural characteristics from baseline to post-treatment time point (approximately 5 weeks interval)
measure: brain electrophysiological characteristics: EEG power in alpha band
timeFrame: changes of alpha band from baseline to post-treatment time point (approximately 5 weeks interval)
measure: brain electrophysiological characteristics: EEG power in theta band
timeFrame: changes of theta band from baseline to post-treatment time point (approximately 5 weeks interval)
measure: brain electrophysiological characteristics: EEG power in beta band
timeFrame: changes of beta band from baseline to post-treatment time point (approximately 5 weeks interval)
measure: brain electrophysiological characteristics: EEG power in delta band
timeFrame: changes of delta band from baseline to post-treatment time point (approximately 5 weeks interval)
Locations:
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
Study officials:
References:
citation: Wang Y, Hardy SJ, Ichesco E, Zhang P, Harris RE, Darbari DS. Alteration of grey matter volume is associated with pain and quality of life in children with sickle cell disease. Transl Res. 2022 Feb;240:17-25. doi: 10.1016/j.trsl.2021.08.004. Epub 2021 Aug 19.
citation: TJ Barrett, A Pucka, B Reyes, SA Jacob, ARW O'Brien, RE Harris, SE Harte, Y Wang*. Acupuncture Alleviates Pain and Improves Quality of Life in Patients with Sickle Cell Disease. Blood. (2022);140 (Supplement 1):5444-5445. (https://doi.org/10.1182/blood-2022-169013)
citation: JX Yao, ARW O'Brien, YJ Tong*, Y Wang*. A Novel Finding in Cerebral Blood Flow in Patients with Sickle Cell Disease Using Bold Functional MRI. Blood (2022) 140 (Supplement 1): 5433-5434. (https://doi.org/10.1182/blood-2022-167594)
citation: SM Park, YY Ji, S Kwon, ARW O'Brien, Y Wang*, YL Kim*. Association of Noninvasive Peripheral Blood Hemoglobin Assessments with Venous Blood Draws Among Sickle Cell Patients. Blood (2022) 140 (Supplement 1): 7832-7833. (https://doi.org/10.1182/blood-2022-165132)