Biometric and Biological Data for Diagnosis and Therapy of Pain Patients

Small Fiber Neuropathy Clinical Trial

— Bio2Treat  

Official title:

Biometric and Biological Data for Diagnosis and Therapy of Pain Patients German: Biometrische Und Biologische Daten für Die Diagnose Und Therapie Bei Schmerzpatienten

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04835779
• Other study ID #: 18-018
• Status: Recruiting
• Start date: October 10, 2020
• Est. completion date: October 2023

Study information

• Verified date: January 2023
• Source: RWTH Aachen University
• Contact: Roman Rolke, Prof. Dr.
• Phone: +49 241 8080880
• Email: rrolke[@]ukaachen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In order to meet the challenge of an unambiguous diagnosis and effective therapy of SFN or the prognosis of susceptibility to the development of SFN, this project aims to create a data basis on which software will be developed during the project. This software should later be able to combine (integrate) quantifiable biometric data collected from the patient (both objectively measured and patient reported parameters) with the results of biological analyses of the patient's own nerve cells from stem cells. We expect that the patient-specific combination and correlation of biometric and biological data can lead to a significant improvement in the diagnosis, prognosis and therapy of chronic pain. The initial data collection required for the development of such a software (Bio2Integrate) will be carried out in three different project parts: Bio2Watch, Bio2Patient and Bio2Cell

Description:

Bio2Watch: In this clinical project part biometric patient data of 24 SFN patients, 3 cancer patients and 21 subjects (control group) will be collected for a period of one year using a PainWatch. The term PainWatch includes an Apple Watch 5 with iPhone 8 and installed app for pain recording. With the aid of the PainWatch, the personal pain sensation in everyday life is documented and personal data such as the pulse rate and the daily number of steps, as well as environmental data, such as the prevailing air pressure, humidity and temperature are recorded. The aim is to use these data as a basis for initial indications of pain-inducing stimuli or combinations of stimuli.

Bio2Patient: In this clinical project part clinically quantifiable tests are carried out, such as quantitative sensory testing (QST), which examines subjective thermal and mechanical sensory perception and pain thresholds. The goal is to determine a specific pain phenotype. In addition, pain evoked potentials (PREPs) are performed to draw conclusions about the function of thin nerve fibers (pain fibers), including projection to the brain. Supplementary SF-36 pain questionnaires are completed to assess the quality of life.For the pain-evoked potentials (PREPs), a total of 20 additional healthy control subjects are to be included (control group D). Four subjects (2 male, 2 female) from each of the age decades 20-29, 30-39, 40-49, 50-59, 60-69 will be included.

Bio2Cell: In the cell-based project part induced pluripotent stem cells (iPS cells) are produced from blood cells of SFN patients, cancer patients and volunteers. These cells will be differentiated into sensory neurons that are relevant in pain processing, so-called nociceptors. Since these nociceptors are derived from the individual patient, they carry the individual genetic characteristics of the patient. These neurons are then analyzed by multi-electrode arrays (MEA). With this method environmental influences such as temperature and air pressure or drugs on the pathophysiology of the patient's are investigated. The main goal is to simulate the conditions, which lead to pain sensation in the context of Bio2Watch and Bio2Patient.

Bio2Integrate: The results from Bio2Watch, Bio2Patient and Bio2Cell will then flow into the software to be developed during the project. Thus, in addition to the identification of stimuli that stimulate pain as well as a genetic correlation to certain markers will be possible. In addition, the targeted modification of the cellular properties of the patient's own sensory neurons through the application of the chemotherapeutic agent can be investigated. To this end, measurements will be made on the cells before and after the application of the substance and compare them with each other. This is the basis for components of the "machine learning " of the Bio2Integrate software.The results of the clinical subprojects are thus an essential component of Bio2Integrate.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: October 2023
• Est. primary completion date: October 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Group A: Criteria 1-5 Group B: Criteria 2-5 Group C: Criteria 2-6 Group D: Criteria 2-4

1. Small fiber neuropathy (after clinical examination or QST or skin biopsy findings)

2. Legal age

3. Written declaration of consent

4. Persons who are legally competent and mentally capable of following the instructions of the staff

5. Sufficient affinity for independent handling of the technology used (PainWatch incl. the corresponding apps) for daily digital pain recording

6. Imminent initiation of neurotoxic chemotherapy in cancer with solid tumors (preferably of the gastrointestinal tract) There are no plans for follow-up recruitment in case no neuropathy develops after chemo.

Exclusion Criteria:

For all Groups:

1. Persons who are accommodated in an institution by order of the authorities or courts

2. Persons who are in a dependent or employment relationship with the auditor

3. For test persons: Exclusion, if they carry a known pain-relevant genetic variant/mutation or suffer from a chronic pain disorder analogous to migraine or chronic back pain.

Related Conditions & MeSH terms

• Small Fiber Neuropathy

Locations

Country	Name	City	State
Germany	Uniklinik RWTH Aachen, Klinik für Palliativmedizin	Aachen	Nordrhein-Westfalen

Sponsors (2)

Lead Sponsor	Collaborator
RWTH Aachen University	Grünenthal GmbH

Country where clinical trial is conducted

Germany, 

References & Publications (11)

Coluzzi F, Rolke R, Mercadante S. Pain Management in Patients with Multiple Myeloma: An Update. Cancers (Basel). 2019 Dec 17;11(12):2037. doi: 10.3390/cancers11122037. — View Citation

Devigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, Broglio L, Granieri E, Lauria G. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain. 2008 Jul;131(Pt 7):1912-25. doi: 10.1093/brain/awn093. Epub 2008 Jun 4. — View Citation

Dworkin RH, O'Connor AB, Kent J, Mackey SC, Raja SN, Stacey BR, Levy RM, Backonja M, Baron R, Harke H, Loeser JD, Treede RD, Turk DC, Wells CD. Interventional management of neuropathic pain: NeuPSIG recommendations. Pain. 2013 Nov;154(11):2249-2261. doi: 10.1016/j.pain.2013.06.004. Epub 2013 Jun 6. — View Citation

Hansen N, Obermann M, Uceyler N, Zeller D, Mueller D, Yoon MS, Reiners K, Sommer C, Katsarava Z. [Clinical application of pain-related evoked potentials]. Schmerz. 2012 Feb;26(1):8-15. doi: 10.1007/s00482-011-1117-1. German. — View Citation

Jenkinson C, Coulter A, Wright L. Short form 36 (SF36) health survey questionnaire: normative data for adults of working age. BMJ. 1993 May 29;306(6890):1437-40. doi: 10.1136/bmj.306.6890.1437. — View Citation

Lacomis D. Small-fiber neuropathy. Muscle Nerve. 2002 Aug;26(2):173-88. doi: 10.1002/mus.10181. — View Citation

Lee J, Mawla I, Kim J, Loggia ML, Ortiz A, Jung C, Chan ST, Gerber J, Schmithorst VJ, Edwards RR, Wasan AD, Berna C, Kong J, Kaptchuk TJ, Gollub RL, Rosen BR, Napadow V. Machine learning-based prediction of clinical pain using multimodal neuroimaging and autonomic metrics. Pain. 2019 Mar;160(3):550-560. doi: 10.1097/j.pain.0000000000001417. — View Citation

Lefaucheur JP, Ahdab R, Ayache SS, Lefaucheur-Menard I, Rouie D, Tebbal D, Neves DO, Ciampi de Andrade D. Pain-related evoked potentials: a comparative study between electrical stimulation using a concentric planar electrode and laser stimulation using a CO2 laser. Neurophysiol Clin. 2012 Jun;42(4):199-206. doi: 10.1016/j.neucli.2011.12.003. Epub 2012 Jan 20. — View Citation

Meents JE, Bressan E, Sontag S, Foerster A, Hautvast P, Rosseler C, Hampl M, Schuler H, Goetzke R, Le TKC, Kleggetveit IP, Le Cann K, Kerth C, Rush AM, Rogers M, Kohl Z, Schmelz M, Wagner W, Jorum E, Namer B, Winner B, Zenke M, Lampert A. The role of Nav1.7 in human nociceptors: insights from human induced pluripotent stem cell-derived sensory neurons of erythromelalgia patients. Pain. 2019 Jun;160(6):1327-1341. doi: 10.1097/j.pain.0000000000001511. — View Citation

Mucke M, Cuhls H, Radbruch L, Baron R, Maier C, Tolle T, Treede RD, Rolke R. [Quantitative sensory testing]. Schmerz. 2014 Dec;28(6):635-46; quiz 647-8. doi: 10.1007/s00482-014-1485-4. German. — View Citation

Rolke R, Rolke S, Hiddemann S, Mucke M, Cuhls H, Radbruch L, Elsner F, Peuckmann-Post V. [Update palliative pain therapy]. Internist (Berl). 2016 Oct;57(10):959-970. doi: 10.1007/s00108-016-0126-7. German. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PainWatch Data	pulse rate (/min)	12 months
Primary	PainWatch Data	number of steps	12 months
Primary	PainWatch Data	pain perception via App (Questionnaire, pain scale 1-10)	12 months
Primary	Weather Data tracked according to GPS Location	Temperature (°C)	12 months
Primary	Weather Data tracked according to GPS Location	Air pressure (Pa)	12 months
Primary	Weather Data tracked according to GPS Location	Humidity (%)	12 months
Primary	Test result QST	Measurement exclusively above the back of the foot that is clinically more severely affected by the SFN, in a balanced row alternately above the right or left foot; one back of the foot as test site per subject	12 months
Primary	Test result PREP (over the same back of the foot as in QST measurement)	P1 Latency (ms)	12 months
Primary	Test result PREP (over the same back of the foot as in QST measurement)	Peak-to-Peak (microV)	12 months
Primary	Test result PREP (over the same back of the foot as in QST measurement)	Current intensity (mA)	12 months
Primary	Result SF 36 Questionnaire	Result SF 36 Questionnaire (different scales per question)	12months
Primary	Results of the Multi-Electrode Array investigations	Spontaneous activity	12 months
Primary	Results of the Multi-Electrode Array investigations	Synchronicity	12 months
Primary	Results of the Multi-Electrode Array investigations	Field potential properties	12 months
Primary	Results of the Multi-Electrode Array investigations	Activity inducing stimuli	12 months
Primary	Efficiency of reprogramming and differentiation of iPS cells	Success of differentiation will be measured by flow cytometry at around d10 of differentiation. The percentage of p75 (CD271)-expressing cells will be meassured. The differentiation is defined as successful if more than 30% of cells express p75. Only those differentiations will be used for MEA-Recordings.	12 months