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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05950867
Other study ID # EC-2023-115
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date July 28, 2023
Est. completion date June 1, 2026

Study information

Verified date November 2023
Source Universitair Ziekenhuis Brussel
Contact Véronique Bissay, MD,Phd
Phone +32 2 477 68 01
Email veronique.bissay@uzbrussel.be
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

To investigate to what extent chronic axonal length-dependent polyneuropathy (CAP) and/or small-fiber neuropathy (SFN) is part of early non-cardiac manifestations of wild-type TTR cardiac amyloidosis (wtTTR-CA). Consequently, explore whether this could ultimately lead to faster diagnosis and clinical outcome of wild-type TTR cardiac amyloidosis (wtTTR-CA).


Description:

Patients with chronic axonal length-dependent polyneuropathy (CAP) and/or small-fiber neuropathy (SFN) without well-defined cause will be recruited after a neurological standard routine work-up with NCS (Nerve conduction study) test, EMG, and Sudoscan®, previously performed at the neurology department of UZ-Brussel in normal clinical setting. All participants will be invited to the Neurology and Cardiology department for one visit on one day, for the following assessments: Following exams will be performed: - assessment of symptoms, severity, and duration of the polyneuropathy and the use of NTSS-6 and COMPASS31 score for mapping somatosensory and autonomic symptoms - evaluation of objective polyneuropathy signs, using following scales: mPND, NIS - Kansas City Cardiomyopathy Questionnaire (KCCQ) - Electrocardiogram (ECG) - Echocardiography The following retrospective data from the medical file will be analyzed: - assessment of medical history, medical treatment, and demographic data - assessment of laboratory results (and, if applicable, other exams) extracted from the medical file and previously performed in the context of polyneuropathy workup - assessment of previously performed NCV/EMG data and Sudoscan®, extracted from the medical file of the participants.


Recruitment information / eligibility

Status Recruiting
Enrollment 150
Est. completion date June 1, 2026
Est. primary completion date June 1, 2026
Accepts healthy volunteers No
Gender All
Age group 60 Years and older
Eligibility Inclusion Criteria: - Patients with chronic axonal length-dependent polyneuropathy (CAP) and/or small-fiber neuropathy (SFN) without well-defined etiology. - Age: >= 60 years - Male and female gender - Written informed consent Exclusion Criteria: - Known cause of polyneuropathy - Other types of peripheral neuropathy than chronic axonal length-dependent polyneuropathy (CAP) and/or small-fiber neuropathy (SFN). - Patients younger than 60 years

Study Design


Related Conditions & MeSH terms


Intervention

Diagnostic Test:
ECG + echocardiography
Electrocardiogram and echocardiography
Other:
Answering questionnaires
Answering questionnaires about polyneuropathy symptoms (NTSS -6, COMPASS31, NIS, mPND) and also cardialogical symptoms (KCCQ-12).

Locations

Country Name City State
Belgium UZ Brussel Jette Belgium Capital City

Sponsors (1)

Lead Sponsor Collaborator
Universitair Ziekenhuis Brussel

Country where clinical trial is conducted

Belgium, 

References & Publications (27)

Aimo A, Merlo M, Porcari A, Georgiopoulos G, Pagura L, Vergaro G, Sinagra G, Emdin M, Rapezzi C. Redefining the epidemiology of cardiac amyloidosis. A systematic review and meta-analysis of screening studies. Eur J Heart Fail. 2022 Dec;24(12):2342-2351. doi: 10.1002/ejhf.2532. Epub 2022 May 16. — View Citation

Barroso FA, Coelho T, Dispenzieri A, Conceicao I, Waddington-Cruz M, Wixner J, Maurer MS, Rapezzi C, Plante-Bordeneuve V, Kristen AV, Gonzalez-Duarte A, Chapman D, Stewart M, Amass L; THAOS investigators. Characteristics of patients with autonomic dysfunction in the Transthyretin Amyloidosis Outcomes Survey (THAOS). Amyloid. 2022 Sep;29(3):175-183. doi: 10.1080/13506129.2022.2043270. Epub 2022 Apr 22. — View Citation

Bastyr EJ 3rd, Price KL, Bril V; MBBQ Study Group. Development and validity testing of the neuropathy total symptom score-6: questionnaire for the study of sensory symptoms of diabetic peripheral neuropathy. Clin Ther. 2005 Aug;27(8):1278-94. doi: 10.1016/j.clinthera.2005.08.002. — View Citation

Campbell CM, LoRusso S, Dispenzieri A, Kristen AV, Maurer MS, Rapezzi C, Lairez O, Drachman B, Garcia-Pavia P, Grogan M, Chapman D, Amass L; THAOS investigators. Sex Differences in Wild-Type Transthyretin Amyloidosis: An Analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS). Cardiol Ther. 2022 Sep;11(3):393-405. doi: 10.1007/s40119-022-00265-7. Epub 2022 May 18. — View Citation

Conceicao I, de Castro I, Castro J. Correlation between Sudoscan and COMPASS 31: assessment of autonomic dysfunction on hATTR V30M patients. Amyloid. 2019;26(sup1):23. doi: 10.1080/13506129.2019.1582494. No abstract available. — View Citation

D'Amato C, Greco C, Lombardo G, Frattina V, Campo M, Cefalo CMA, Izzo V, Lauro D, Spallone V. The diagnostic usefulness of the combined COMPASS 31 questionnaire and electrochemical skin conductance for diabetic cardiovascular autonomic neuropathy and diabetic polyneuropathy. J Peripher Nerv Syst. 2020 Mar;25(1):44-53. doi: 10.1111/jns.12366. Epub 2020 Feb 14. — View Citation

Dispenzieri A, Coelho T, Conceicao I, Waddington-Cruz M, Wixner J, Kristen AV, Rapezzi C, Plante-Bordeneuve V, Gonzalez-Moreno J, Maurer MS, Grogan M, Chapman D, Amass L; THAOS investigators. Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update. Orphanet J Rare Dis. 2022 Jun 18;17(1):236. doi: 10.1186/s13023-022-02359-w. — View Citation

Dyck PJB, Gonzalez-Duarte A, Obici L, Polydefkis M, Wiesman JF, Antonino I, Litchy WJ, Dyck PJ. Development of measures of polyneuropathy impairment in hATTR amyloidosis: From NIS to mNIS + 7. J Neurol Sci. 2019 Oct 15;405:116424. doi: 10.1016/j.jns.2019.116424. Epub 2019 Aug 8. — View Citation

England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, Asbury AK, Szigeti K, Lupski JR, Latov N, Lewis RA, Low PA, Fisher MA, Herrmann DN, Howard JF Jr, Lauria G, Miller RG, Polydefkis M, Sumner AJ; American Academy of Neurology. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Academy of Physical Medicine and Rehabilitation. Neurology. 2009 Jan 13;72(2):185-92. doi: 10.1212/01.wnl.0000336370.51010.a1. Epub 2008 Dec 3. — View Citation

Gonzalez-Lopez E, Gagliardi C, Dominguez F, Quarta CC, de Haro-Del Moral FJ, Milandri A, Salas C, Cinelli M, Cobo-Marcos M, Lorenzini M, Lara-Pezzi E, Foffi S, Alonso-Pulpon L, Rapezzi C, Garcia-Pavia P. Clinical characteristics of wild-type transthyretin cardiac amyloidosis: disproving myths. Eur Heart J. 2017 Jun 21;38(24):1895-1904. doi: 10.1093/eurheartj/ehx043. — View Citation

Hanewinckel R, Ikram MA, Van Doorn PA. Peripheral neuropathies. Handb Clin Neurol. 2016;138:263-82. doi: 10.1016/B978-0-12-802973-2.00015-X. — View Citation

Kharoubi M, Roche F, Bezard M, Hupin D, Silva S, Oghina S, Chalard C, Zaroui A, Galat A, Guendouz S, Canoui-Poitrine F, Hittinger L, Teiger E, Lefaucheur JP, Damy T. Prevalence and prognostic value of autonomic neuropathy assessed by Sudoscan(R) in transthyretin wild-type cardiac amyloidosis. ESC Heart Fail. 2021 Apr;8(2):1656-1665. doi: 10.1002/ehf2.13131. Epub 2020 Dec 22. — View Citation

Kleefeld F, Scherret E, Knebel F, Messroghli D, Heidecker B, Wetz C, Schatka I, Barzen G, Tschope C, Amthauer H, Hahn K. Same same, but different? The neurological presentation of wildtype transthyretin (ATTRwt) amyloidosis. Amyloid. 2022 Jun;29(2):92-101. doi: 10.1080/13506129.2021.2014448. Epub 2022 Jan 7. — View Citation

Koike H, Okumura T, Murohara T, Katsuno M. Multidisciplinary Approaches for Transthyretin Amyloidosis. Cardiol Ther. 2021 Dec;10(2):289-311. doi: 10.1007/s40119-021-00222-w. Epub 2021 Jun 4. — View Citation

Lehmann HC, Wunderlich G, Fink GR, Sommer C. Diagnosis of peripheral neuropathy. Neurol Res Pract. 2020 Jul 15;2:20. doi: 10.1186/s42466-020-00064-2. eCollection 2020. — View Citation

Li Y. Axonal Sensorimotor Polyneuropathies. Continuum (Minneap Minn). 2017 Oct;23(5, Peripheral Nerve and Motor Neuron Disorders):1378-1393. doi: 10.1212/CON.0000000000000514. — View Citation

Lindmark K, Pilebro B, Sundstrom T, Lindqvist P. Prevalence of wild type transtyrethin cardiac amyloidosis in a heart failure clinic. ESC Heart Fail. 2021 Feb;8(1):745-749. doi: 10.1002/ehf2.13110. Epub 2020 Nov 17. — View Citation

Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB, Rapezzi C; ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):1007-1016. doi: 10.1056/NEJMoa1805689. Epub 2018 Aug 27. — View Citation

Papagianni A, Ihne S, Zeller D, Morbach C, Uceyler N, Sommer C. Clinical and apparative investigation of large and small nerve fiber impairment in mixed cohort of ATTR-amyloidosis: impact on patient management and new insights in wild-type. Amyloid. 2022 Mar;29(1):14-22. doi: 10.1080/13506129.2021.1976751. Epub 2021 Oct 11. — View Citation

Russell A, Hahn C, Chhibber S, Korngut L, Fine NM. Utility of Neuropathy Screening for Wild-Type Transthyretin Amyloidosis Patients. Can J Neurol Sci. 2021 Sep;48(5):607-615. doi: 10.1017/cjn.2020.271. Epub 2020 Dec 21. — View Citation

Sperry BW, Reyes BA, Ikram A, Donnelly JP, Phelan D, Jaber WA, Shapiro D, Evans PJ, Maschke S, Kilpatrick SE, Tan CD, Rodriguez ER, Monteiro C, Tang WHW, Kelly JW, Seitz WH Jr, Hanna M. Tenosynovial and Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-2050. doi: 10.1016/j.jacc.2018.07.092. — View Citation

Vianello PF, La Malfa G, Tini G, Mazzola V, Miceli A, Santolini E, Briano S, Porto I, Canepa M. Prevalence of transthyretin amyloid cardiomyopathy in male patients who underwent bilateral carpal tunnel surgery: The ACTUAL study. Int J Cardiol. 2021 Apr 15;329:144-147. doi: 10.1016/j.ijcard.2020.12.044. Epub 2020 Dec 30. — View Citation

Wajnsztajn Yungher F, Kim A, Boehme A, Kleyman I, Weimer LH, Maurer MS, Brannagan TH 3rd. Peripheral neuropathy symptoms in wild type transthyretin amyloidosis. J Peripher Nerv Syst. 2020 Sep;25(3):265-272. doi: 10.1111/jns.12403. Epub 2020 Jul 27. — View Citation

Westin O, Fosbol EL, Maurer MS, Leicht BP, Hasbak P, Mylin AK, Rorvig S, Lindkaer TH, Johannesen HH, Gustafsson F. Screening for Cardiac Amyloidosis 5 to 15 Years After Surgery for Bilateral Carpal Tunnel Syndrome. J Am Coll Cardiol. 2022 Sep 6;80(10):967-977. doi: 10.1016/j.jacc.2022.06.026. — View Citation

Zegri-Reiriz I, de Haro-Del Moral FJ, Dominguez F, Salas C, de la Cuadra P, Plaza A, Krsnik I, Gonzalez-Lopez E, Garcia-Pavia P. Prevalence of Cardiac Amyloidosis in Patients with Carpal Tunnel Syndrome. J Cardiovasc Transl Res. 2019 Dec;12(6):507-513. doi: 10.1007/s12265-019-09895-0. Epub 2019 Jun 18. — View Citation

Ziemssen T, Siepmann T. The Investigation of the Cardiovascular and Sudomotor Autonomic Nervous System-A Review. Front Neurol. 2019 Feb 12;10:53. doi: 10.3389/fneur.2019.00053. eCollection 2019. — View Citation

Zis P, Sarrigiannis PG, Rao DG, Hewamadduma C, Hadjivassiliou M. Chronic idiopathic axonal polyneuropathy: a systematic review. J Neurol. 2016 Oct;263(10):1903-10. doi: 10.1007/s00415-016-8082-7. Epub 2016 Mar 9. — View Citation

* Note: There are 27 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary Primary Outcome: Evaluation of prevalence of wild-type cardiac amyloidosis in our CAP and/or SFN population without well known cause. Prevalence of cardiac amyloidosis by doing a cardiac screening for wild-type cardiac amyloidosis with performing an echocardiography.
Echocardiography criteria: LV wall (>12mm), left ventricular ejection fraction (%), Apical sparing pattern (y/n), diastolic dysfunction (y/n), left atrial volume (ml/m2).
Left atrial volume in ml and LA volume in ml/m2, whereby m2 is the body surface area based on weight and height (Mosteller formula).
36 months
Primary Primary Outcome: Evaluation of prevalence of wild-type cardiac amyloidosis in our CAP and/or SFN population without well known cause Prevalence of cardiac amyloidosis by doing a cardiac screening for wild-type cardiac amyloidosis with performing an ECG.
ECG criteria: atrial fibrillation (y/n), QRS-duration, low voltage (y/n)
36 months
Primary Primary Outcome: Evaluation of prevalence of wild-type cardiac amyloidosis in our CAP and/or SFN population without well known cause Prevalence of cardiac amyloidosis by doing a cardiac screening for wild-type cardiac amyloidosis with performing a questionnaire (Kansas City Cardiomyopathy Questionnaire).
KCCQ-12 has 4 domains (Physical Limitation Score, Symptom Frequency Score, Quality of Life Score, Social Limitation Score) and one Summary Score. Scores are scaled 0-100, where 0 denotes the lowest reportable health status and 100 the highest.
This descriptive score will be used as a functional parameter without a cut-off.
36 months
Secondary Secondary outcome: severity and evolution Considering the rather small study population and the rarity of wtTTR amyloidosis, statistical analyses cannot be used without massively overfitting the results, which will not be reproducible. The investigators consequently opt for descriptive statistics to compare the group of polyneuropathy patients with wt-Ca and those without wt-CA. Therefore a few parameters are examined. The first scale used therefore is the modified Polyneuropathy Disability score (mPND). This scale is a questionnaire with a few questions about the complaints of the polyneuropathy in the daily life. O means no complaints of the polyneuropathy in daily life, IV means a major impact on the daily life of the patient. 36 months
Secondary Secondary outcome: severity and evolution Considering the rather small study population and the rarity of wtTTR amyloidosis, statistical analyses cannot be used without massively overfitting the results, which will not be reproducible.
The investigators consequently opt for descriptive statistics to compare the group of polyneuropathy patients with wt-Ca and those without wt-CA. Therefore a few parameters are examined. The second scale used therefore is the Neuropathy Impairment Score (NIS).This scale is a questionnaire with a few questions about the complaints of the polyneuropathy in the daily life. The score is between 0 and 244. O means less complaints in the daily life, 244 means major impact in the daily life of the patient.
36 months
Secondary Secondary outcome: severity and evolution Considering the rather small study population and the rarity of wtTTR amyloidosis, statistical analyses cannot be used without massively overfitting the results, which will not be reproducible.
The investigators consequently opt for descriptive statistics to compare the group of polyneuropathy patients with wt-Ca and those without wt-CA. Therefore a few parameters are examined. The third scale used therefore is the Neuropathy Total Symptom Score - Health Care professional administered version (NTSS-6). This scale is a questionnaire with a few items about the symptoms of the polyneuropathy in the daily life (aching pain, burning pain, prickling sensation, numbness, lancinating pain and allodynia). Depending on the presence of the symptoms in time and strength, a score will show up. On each symptom you can score a maximum of 3,66. So the total score for this scale is 21,96 if the patients has major complaints in daily life.
36 months
Secondary Secondary outcome: severity and evolution Considering the rather small study population and the rarity of wtTTR amyloidosis, statistical analyses cannot be used without massively overfitting the results, which will not be reproducible.
The investigators consequently opt for descriptive statistics to compare the group of polyneuropathy patients with wt-Ca and those without wt-CA. Therefore a few parameters are examined. The fourth scale used therefore is the Composite Autonomic Symptom score (COMPASS-31). This scale is a questionnaire with a 31 questions about the complaints in the daily life and also if there complaints/symptoms on the autonomic system. A few questions are asked about different domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal system, bladder, pupillomotor).The total score is minimal 0 and maximal 75 raw counted (100 weighted).Each domain had a weighting factor to be count depending on the answers of the patient.
36 months
Secondary Secondary outcome: red flags that could increase the awareness of neurologists for wild-type TTR-cardiac amyloidosis The red flags for wild-type TTR cardiac amyloidosis are among others carpal tunnel syndrome (CTS), wich can be detected by performing an electromyography (EMG). 36 months
Secondary Secondary outcome: red flags that could increase the awareness of neurologists for wild-type TTR-cardiac amyloidosis The red flags for wild-type TTR cardiac amyloidosis are among others spinal canal stenosis. 36 months
Secondary Secondary outcome: red flags that could increase the awareness of neurologists for wild-type TTR-cardiac amyloidosis The red flags for wild-type TTR cardiac amyloidosis are among others trigger finger. 36 months
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