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Completed

NCT Number: NCT06414746

Hereditary Transthyretin Amyloidosis Polyneuropathy in Patients With Carpal Tunnel Syndrome in Russia

This is a multicenter observational study consisting of retrospective and prospective phases. The retrospective phase will entail secondary data collection from electronic or paper medical records of patients who underwent surgery for CTS to assess their probability of having ATTR PN.

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Key information

Conditions

Hereditary Transthyretin Amyloidosis Amyloidosis Amyloidosis, Hereditary, Transthyretin-Related Carpal Tunnel Syndrome Cumulative Trauma Disorders Median Neuropathy Metabolic Diseases Mononeuropathies Nerve Compression Syndromes Nervous System Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Peripheral Nervous System Diseases Polyneuropathies Polyneuropathy Proteostasis Deficiencies Sprains and Strains Wounds and Injuries

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Research Site, Arkhangelsk, Russia

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About this study

ATTR PN is a genotypically, phenotypically and geographically variable disease with a poor prognosis, albeit available disease-modifying drugs can change the disease trajectory. Thus country-specific epidemiologic data collection and identification of early stage PN, including previously misdiagnosed patients, is crucial to improve outcomes and quality of life. However, no observational studies on the epidemiology of ATTR PN in the whole Russian population, or in patients with CTS, have been performed.

Therefore, there is a need to conduct a large-scale observational study to determine the prevalence of ATTR PN in Russia, obtain information on patients' clinical characteristics, and determine their medical needs.

The approaches to diagnosis of ATTR PN in Russia over the past few years have been characterized by the use of heterogenous methods, partially explained by the lack of availability of molecular genetic testing, which is essential to diagnose the presence of pathogenic mutation in patients with hereditary ATTR PN. Thus, recent introduction of such tests into routine clinical practice may allow to assess reliable epidemiologic data including estimation of true ATTR PN prevalence among patients with CTS, which can often be the first manifestation of the disease. Earlier recognition, in turn, may lead to timely treatment initiation and change in the prognostic outlook of ATTR PN patients.

In order to assess the prevalence of ATTR PN in patients undergoing surgery for CTS in Russia this study will retrospectively include patients with the diagnosis of CTS undergoing surgery between the 1st January 2021 and the 1st September 2024. Suspicion of ATTR PN will be assessed in each case, and diagnostic tests (comprehensive neurological examination including nerve conduction study (NCS) combined with molecular genetic testing) to confirm or exclude the disease will be conducted prospectively in eligible patients. In addition to that, clinical features, concomitant manifestations, and diagnosed genotypes will be analyzed to examine characteristic ATTR PN patient profiles in the Russian Federation.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for the retrospective phase are:

  • Patients with the established diagnosis of CTS.
  • Bilateral involvement of carpal tunnel established between the 1st January 2021 and the 31st December 2024 (both patients who underwent CTS surgical intervention and without it are enrolled).
  • Age ≥ 18 years at the time of CTS diagnosis.
  • Provided written informed consent for the prospective phase of the study (including molecular genetic testing).
  • Presence of ≥1 of the following features (red flags):

a. CIDP or polyneuropathy of unknown etiology in the family history; b. Spinal canal stenosis of the lumbar region; c. Autonomic dysfunction, defined by the presence of ≥1 of the following symptoms - i. Gastrointestinal complaints (constipation, chronic diarrhea, or both); ii. Erectile dysfunction; iii. Orthostatic hypotension; d. Gait disorders; e. Sweating disorders, anhidrosis. f. Paresthesia and burning of the skin of the distal extremities g. Distal symmetrical paresis h. Hypotrophy and hypotension of limb muscles, areflexia i. Biceps tendon rupture j. Aortic valve stenosis k. Diagnosis of HFpEF

l. Unexplained weight loss ≥5 kilos at any timepoint since the onset of symptoms of CTS; m. Left ventricular hypertrophy (based on electro- or echocardiographic criteria documented in the patient's medical record); n. Heart rhythm disorders; o. Renal abnormalities, defined by ≥1 of the following features - i. Documented diagnosis of chronic kidney disease (CKD); ii. Decreased estimated glomerular filtration rate (eGFR <60 mL/min/1.73m2); iii. Increased serum creatinine (SCr) above reference range of the local laboratory; iv. Albuminuria (≥30 mg/g of creatinine or ≥30 mg/24h); v. Proteinuria (according to urinalysis results); p. Ophthalmology disorder defined by ≥1 of the following features - i. Vitreous body inclusions (opacification); ii. Glaucoma; iii. Pupillary disorders; iv. Vitrectomy

  • Absence of previously established ATTR PN diagnosis (ICD-10 code Е85.1, "Neuropathic hereditary familial amyloidosis").

Exclusion criteria

  • Participation in any interventional trial within the period since identification of bilateral involvement of carpal tunnel until the end of current study.

The following criteria apply for non-inclusion of patients into the prospective part of the study:

  • Previously performed TTR genetic testing;
  • Verified B12 deficiency;
  • History of alcohol abuse according to the patient's medical record.

Treatment and study plan

Primary outcomes

  1. To define the prevalence of ATTR PN in patients diagnosed with CTS and having bilateral involvement in routine clinical practice in the Russian Federation.

    Time frame: Up to 12 months

    In order to achieve primary objective, the proportion of patients with confirmed diagnosis of ATTR PN (presence of TTR gene mutation according to the results of molecular genetic testing and clinical symptoms and/or signs of polyneuropathy) among those diagnosed with CTS and having bilateral involvement will be calculated.

Secondary outcomes

  1. To assess general demographic characteristics of patients with ATTR PN in Russia - Mean age (years) at the onset of CTS symptoms

    Time frame: up to 12 months

  2. To assess general demographic characteristics of patients with ATTR PN in Russia: Mean age (years) at the onset of polyneuropathy symptoms

    Time frame: up to 12 months

  3. to assess general demographic characteristics of patients with ATTR PN in Russia: Proportion of patients with late (>50 years) diagnosis of ATTR PN

    Time frame: up to 12 months

  4. to assess general demographic characteristics of patients with ATTR PN in Russia: Mean age (years) at the time of CTS surgery

    Time frame: up to 12 months

  5. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Number and proportion of patients with specific characteristics of the first and repeat CTS surgery

    Time frame: up to 12 months

    • Left hand;
    • Right hand;
    • Both hands;

  6. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Proportion of patients with CTS recurrence after surgery

    Time frame: up to 12 months

  7. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Proportion of patients undergoing repeat surgery for CTS after the index operation

    Time frame: up to 12 months

  8. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Proportion of patients with PN progression after surgery

    Time frame: up to 12 months

  9. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Proportion of patients with different number of red flags:

    Time frame: up to 12 months

    • 1 red flag;
    • 2 red flags;
    • 3 red flags;
    • 4-5 red flags;
    • 6-10 red flags;
    • >10 red flags;

  10. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Mean age (years) at ATTR PN diagnosis

    Time frame: up to 12 months

  11. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Proportion of women and men

    Time frame: up to 12 months

  12. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Mean body mass index (BMI) and proportion of patients with different BMI dimensions at the time of CTS diagnosis and at Visit 1:

    Time frame: up to 12 months

    • Underweight (BMI <18.5 kg/m2);
    • Normal weight (BMI ≥18.5 and <25 kg/m2);
    • Overweight (BMI ≥25 and <30 kg/m2);
    • Obesity (BMI ≥30 kg/m2)

  13. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Proportion of patients with a history of unexplained weight loss (≥5 kg) at any point since CTS diagnosis

    Time frame: up to 12 months

  14. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Mean and median time from CTS symptom onset (months) to ATTR PN diagnosis

    Time frame: up to 12 months

  15. To assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Median number of physicians seen since symptom onset before the correct ATTR PN diagnosis

    Time frame: up to 12 months

  16. To assess general demographic and clinical characteristics of patients with ATTR PN in Russia: Median number of hospitalizations for PN before the correct ATTR PN diagnosis

    Time frame: up to 12 months

  17. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Number and proportion of patients with previously established incorrect diagnosis according to medical records, specifically with:

    Time frame: up to 12 months

    • CIDP;
    • Lumbar/sacral radiculopathy;
    • Lumbar canal stenosis;
    • Paraproteinaemic peripheral neuropathy;
    • Chronic progressive sensory/sensorimotor axonal idiopathic PN;
    • AL amyloidosis;
    • Fibromyalgia;
    • Other (specify)

  18. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN: Proportion of patients with family history of neuropathic disease

    Time frame: up to 12 months

  19. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN: Proportion of patients with specific peripheral neurological manifestations:

    Time frame: up to 12 months

    • Neuropathic pain (allodynia, hyperalgesia);
    • Progressive sensory disturbances (loss of temperature, pain, other sensation);
    • Paresthesia, dysesthesia;
    • Progressive motor disturbances;
    • Walking difficulty, gait disorder;
    • Balance disorder

  20. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN: Proportion of patients with specific Polyneuropathy Disability (PND) classes:

    Time frame: up to 12 months

    • 0;
    • I;
    • II;
    • IIIA;
    • IIIB;
    • IV;

  21. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - Proportion of patients with specific distribution of polyneuropathy symptoms:

    Time frame: up to 12 months

    • Upper-limb;
    • Lower-limb;
    • Both upper-limb and lower-limb

  22. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - Number of patients with autonomic neurological manifestations, including specifically:

    Time frame: up to 12 months

    • Orthostatic hypotension;
    • Syncope;
    • Gastrointestinal motility disorders - i. Constipation; ii. Early satiety; iii. Diarrhea; iv. Nausea, vomiting;
    • Erectile dysfunction;
    • Neurogenic bladder;
    • Recurrent urinary infections;
    • Anhidrosis;

  23. To describe data on the presence of cardiovascular, neurological and other comorbidities- Number and proportion of patients taking specific groups of cardiovascular medications at the time of CTS diagnosis and at the time of prospective visit:

    Time frame: up to 12 months

    • Left ventricular hypertrophy;
    • Left bundle branch block;
    • Atrioventricular block;
    • Heart failure with preserved ejection fraction;
    • Elevated serum N-terminal-proB-type natriuretic peptide (NT-proBNP) concentration;
    • Cardiac valve stenosis;
    • Cardiac valve regurgitation;
    • Tachyarrhythmia;
    • Other (specify);
    • None;

  24. Number of patients taking specific groups of cardiovascular medications at the time of CTS surgery and at the time of prospective visit:

    Time frame: up to 12 months

    • Angiotensin converting enzyme inhibitor (ACEI) (specify);
    • Angiotensin receptor blocker (ARB) (specify);
    • Angiotensin receptor and neprilysin inhibitor (ARNI);
    • Sodium-glucose transporter type 2 inhibitor (SGLT2i) (specify);
    • Mineralocorticoid receptor antagonist (MRA) (specify);
    • Beta-blocker (specify);
    • Diuretic (specify);
    • Other cardiovascular (CV) medications (specify);
    • Other (specify);

  25. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - Number of patients with concomitant ophthalmologic manifestations, including specifically

    Time frame: up to 12 months

    • Vitreous body inclusions (opacification);
    • Glaucoma;
    • Abnormal conjunctival vessels;
    • Papillary abnormalities;
    • Dry eye;
    • Other (specify);

  26. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - Number of patients with concomitant musculoskeletal manifestations, including specifically:

    Time frame: up to 12 months

    • Spinal stenosis;
    • Osteoarthritis, including hip and knee arthroplasty;
    • Trigger finger;
    • Charcot's joints;
    • Biceps tendon rupture;
    • Rotator cuff injury;
    • Other (specify);

  27. Mean and median serum NT-proBNP (pg/ml) concentration

    Time frame: up to 12 months

  28. Proportion of patients with laboratory confirmed paraproteinemia

    Time frame: up to 12 months

  29. Mean and median urine albumin-creatinine ratio (UACR, mg/g of creatinine)

    Time frame: up to 12 months

  30. Proportion of patients with diagnosed CKD, including specifically

    Time frame: up to 12 months

    • Stage C1;
    • Stage C2;
    • Stage C3a;
    • Stage C3b;
    • Stage C4;
    • Stage C5;

  31. Number of patients with concomitant renal dysfunction, including specifically

    Time frame: up to 12 months

    • Elevated SCr level (based on the local laboratory reference range);
    • Decreased eGFR (<60 ml/min/1.73m2);
    • Presence of albuminuria (≥30 mg/g creatinine (≥30 mg/g of creatinine or ≥30 mg/24h);
    • Presence of proteinuria (according to urinalysis results);
    • Ultrasound signs of amyloid nephropathy;

  32. Number of patients with confirmed length-dependent peripheral sensory-motor neuropathy based on NCS results

    Time frame: up to 12 months

  33. Mean and median measured peripheral sensory nerve conduction velocities

    Time frame: up to 12 months

    • Left Medial;
    • Left Ulnar;
    • Left Sural;
    • Right Medial;
    • Right Ulnar;
    • Right Sural;

  34. Number of patients with reduced peripheral sensory nerve conduction velocity at ≥1 site

    Time frame: up to 12 months

  35. Mean and median measured peripheral motor nerve conduction velocities

    Time frame: up to 12 months

    • Left Medial;
    • Left Ulnar;
    • Left Tibial;
    • Left Peroneal;
    • Right Medial;
    • Right Ulnar;
    • Right Tibial;
    • Right Peroneal;

  36. Number of patients with reduced motor sensory nerve conduction velocity at ≥1 site

    Time frame: up to 12 months

  37. Mean and median measured sensory action potential (SAP) amplitudes

    Time frame: up to 12 months

    • Left Medial;
    • Left Ulnar;
    • Left Sural;
    • Right Medial;
    • Right Ulnar;
    • Right Sural

  38. Number of patients with reduced/absent SAP amplitude at ≥1 site

    Time frame: up to 12 months

  39. Mean and median measured distal compound muscle action potential (dCMAP) amplitudes

    Time frame: up to 12 months

    • Left Medial;
    • Left Ulnar;
    • Left Tibial;
    • Left Peroneal;
    • Right Medial;
    • Right Ulnar;
    • Right Tibial;
    • Right Peroneal

  40. Mean and median measured proximal compound muscle action potential (pCMAP) amplitudes

    Time frame: up to 12 months

    • Left Medial;
    • Left Ulnar;
    • Left Tibial;
    • Left Peroneal;
    • Right Medial;
    • Right Ulnar;
    • Right Tibial;
    • Right Peroneal

  41. Number of patients with reduced/absent dCMAP amplitude at ≥1 site

    Time frame: up to 12 months

  42. Number of patients with reduced/absent pCMAP amplitude at ≥1 site

    Time frame: up to 12 months

  43. Proportion of patients with each score by each parameter of neurological examination

    Time frame: up to 12 months

  44. Number of patients in the specific categories of the modified Rankin scale

    Time frame: up to 12 months

    • Score 1 (no significant disability);
    • Score 2 (slight disability);
    • Score 3 (moderate disability);
    • Score 4 (moderately severe disability);
    • Score 5 (severe disability);

  45. Proportion of patients with specific number of points according to Inflammatory Neuropathy Cause and Treatment (INCAT) upper extremity scale

    Time frame: up to 12 months

    • 0 points;
    • 1 point;
    • 2 points;
    • 3 points;
    • 4 points;
    • 5 points

  46. Median number of points according to INCAT upper extremity scale

    Time frame: up to 12 months

  47. Proportion of patients with specific number of points according to INCAT lower extremity scale

    Time frame: up to 12 months

    • 0 points;
    • 1 point;
    • 2 points;
    • 3 points;
    • 4 points;
    • 5 points

  48. Median number of points according to INCAT lower extremity scale

    Time frame: up to 12 months

  49. Mean and median number of points according to combined clinical and electrophysiological score

    Time frame: up to 12 months

  50. To describe data on the results of genetic testing for ATTR in CTS patients undergoing surgery:Number and proportion of patients with specific TTR gene mutations

    Time frame: up to 12 months

    • Val30Met;
    • Ile107Val;
    • Phe33Leu;
    • Ala81Val;
    • Ser23Asn;
    • Ala25Thr;
    • Val32Ala;
    • Thr40Asn;
    • Gly47Ala;
    • Glu54Gln;
    • Tyr69Phe;
    • Glu92Lys;
    • Thr119Met;
    • Other

  51. to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Proportion of patients with previously established incorrect diagnosis according to medical records, specifically with:

    Time frame: up to 12 months

    • CIDP;
    • Lumbar/sacral radiculopathy;
    • Lumbar canal stenosis;
    • Paraproteinaemic peripheral neuropathy;
    • Chronic progressive sensory/sensorimotor axonal idiopathic PN;
    • AL amyloidosis;
    • Fibromyalgia;
    • Other (specify);

  52. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - proportion of patients with autonomic neurological manifestations, including specifically:

    Time frame: up to 12 months

    manifestations, including specifically:

    • Orthostatic hypotension;
    • Syncope;
    • Gastrointestinal motility disorders - i. Constipation; ii. Early satiety; iii. Diarrhea; iv. Nausea, vomiting;
    • Erectile dysfunction;
    • Neurogenic bladder;
    • Recurrent urinary infections;
    • Anhidrosis;

  53. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - proportion of patients with concomitant cardiac manifestations, including specifically:

    Time frame: up to 12 months

    • Left ventricular hypertrophy;
    • Left bundle branch block;
    • Atrioventricular block;
    • Heart failure with preserved ejection fraction;
    • Elevated serum N-terminal-proB-type natriuretic peptide (NT-proBNP) concentration;
    • Cardiac valve stenosis;
    • Cardiac valve regurgitation;
    • Tachyarrhythmia;
    • Other (specify);
    • None;

  54. proportion of patients taking specific groups of cardiovascular medications at the time of CTS surgery and at the time of prospective visit:

    Time frame: up to 12 months

    • Angiotensin converting enzyme inhibitor (ACEI) (specify);
    • Angiotensin receptor blocker (ARB) (specify);
    • Angiotensin receptor and neprilysin inhibitor (ARNI);
    • Sodium-glucose transporter type 2 inhibitor (SGLT2i) (specify);
    • Mineralocorticoid receptor antagonist (MRA) (specify);
    • Beta-blocker (specify);
    • Diuretic (specify);
    • Other cardiovascular (CV) medications (specify);
    • Other (specify);

  55. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - proportion of patients with concomitant ophthalmologic manifestations, including specifically

    Time frame: up to 12 months

    • Vitreous body inclusions (opacification);
    • Glaucoma;
    • Abnormal conjunctival vessels;
    • Papillary abnormalities;
    • Dry eye;
    • Other (specify);

  56. To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - proportion of patients with concomitant musculoskeletal manifestations, including specifically:

    Time frame: up to 12 months

    • Spinal stenosis;
    • Osteoarthritis, including hip and knee arthroplasty;
    • Trigger finger;
    • Charcot's joints;
    • Biceps tendon rupture;
    • Rotator cuff injury;
    • Other (specify);

  57. proportion of patients with concomitant renal dysfunction, including specifically

    Time frame: up to 12 months

    • Elevated SCr level (based on the local laboratory reference range);
    • Decreased eGFR (<60 ml/min/1.73m2);
    • Presence of albuminuria (≥30 mg/g creatinine (≥30 mg/g of creatinine or ≥30 mg/24h);
    • Presence of proteinuria (according to urinalysis results);
    • Ultrasound signs of amyloid nephropathy;

  58. proportion of patients with confirmed length-dependent peripheral sensory-motor neuropathy based on NCS results

    Time frame: up to 12 months

  59. proportion of patients with reduced peripheral sensory nerve conduction velocity at ≥1 site

    Time frame: up to 12 months

  60. proportion of patients with reduced motor sensory nerve conduction velocity at ≥1 site

    Time frame: up to 12 months

  61. proportion of patients with reduced/absent SAP amplitude at ≥1 site

    Time frame: up to 12 months

  62. proportion of patients with reduced/absent dCMAP amplitude at ≥1 site

    Time frame: up to 12 months

  63. proportion of patients with reduced/absent pCMAP amplitude at ≥1 site

    Time frame: up to 12 months

  64. proportion of patients in the specific categories of the modified Rankin scale

    Time frame: up to 12 months

    -a) Score 1 (no significant disability); b) Score 2 (slight disability); c) Score 3 (moderate disability); d) Score 4 (moderately severe disability); e) Score 5 (severe disability

  65. To assess general demographic characteristics of patients with ATTR PN in Russia - Mean age (years) at the primary CTS diagnosis

    Time frame: up to 12 months

  66. To assess general demographic characteristics of patients with ATTR PN in Russia - Mean age (years) at the identification of bilateral involvement

    Time frame: up to 12 months

  67. To assess general demographic characteristics of patients with ATTR PN in Russia - Mean age (years) at ATTR PN diagnosis

    Time frame: up to 12 months

  68. To assess general demographic characteristics of patients with ATTR PN in Russia -Proportion of patients underwent CTS surgery (i.e. at least one surgery)

    Time frame: up to 12 months

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

A Multicenter Observational Retrospective-prospective Study of Prevalence, Clinical Characteristics of Hereditary Transthyretin Amyloidosis Polyneuropathy in Russian Patients Undergoing Surgery for CTS in Real Clinical Practice

Acronym: LOCUS

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
May 16, 2024
Registry last updated
Jun 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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