- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06414746
Hereditary Transthyretin Amyloidosis Polyneuropathy in Patients With Carpal Tunnel Syndrome in Russia (LOCUS)
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
Study Overview
Status
Detailed Description
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.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: AstraZeneca Clinical Study Information Center
- Phone Number: 1-877-240-9479
- Email: information.center@astrazeneca.com
Study Locations
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-
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Moscow, Russian Federation
- Recruiting
- Research Site
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Saint-Petersburg, Russian Federation, 194354
- Recruiting
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
for the retrospective phase are:
- Patients with the established diagnosis of CTS undergoing surgical intervention between the 1st January 2021 and the 1st September 2024.
Age ≥ 18 years at the time of surgery.
Additional inclusion criteria for the prospective phase are:
- Provided written informed consent for the prospective phase of the study (including molecular genetic testing).
- Bilateral CTS;
Presence of ≥1 of the following features (red flags):
- CIDP or polyneuropathy of unknown etiology in the family history;
- Spinal canal stenosis of the lumbar region;
- 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;
- Gait disorders;
- Sweating disorders, anhidrosis.
- Paresthesia and burning of the skin of the distal extremities
- Distal symmetrical paresis
- Hypotrophy and hypotension of limb muscles, areflexia
- Biceps tendon rupture
- Aortic valve stenosis
- Diagnosis of HFpEF
- Unexplained weight loss ≥5 kilos at any timepoint since the onset of symptoms of CTS;
- Left ventricular hypertrophy (based on electro- or echocardiographic criteria documented in the patient's medical record);
- Heart rhythm disorders;
- 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).
- 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:
for the retrospective phase are:
Participation in any interventional trial within the period since surgical intervention until the end of current study.
Additional exclusion criteria for the prospective phase are:
- Previously performed TTR genetic testing;
- Verified B12 deficiency;
- History of alcohol abuse according to the patient's medical record.
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To define the prevalence of ATTR PN in patients undergoing surgery for CTS 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 who underwent surgery for CTS will be calculated.
|
Up to 12 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
up to 12 months
|
|
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
|
up to 12 months
|
|
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
|
up to 12 months
|
|
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
|
up to 12 months
|
|
to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Number and proportion of patients with specific characteristic of index CTS download
Time Frame: up to 12 months
|
|
up to 12 months
|
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
|
up to 12 months
|
|
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
|
up to 12 months
|
|
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
|
up to 12 months
|
|
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
|
|
up to 12 months
|
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
|
up to 12 months
|
|
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
|
up to 12 months
|
|
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 surgery and at Visit 1:
Time Frame: up to 12 months
|
|
up to 12 months
|
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 symptom onset
Time Frame: up to 12 months
|
up to 12 months
|
|
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
|
up to 12 months
|
|
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
|
up to 12 months
|
|
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
|
up to 12 months
|
|
to assess general demographic and clinical characteristics of patients with ATTR PN in Russia - Number of patients with previously established incorrect diagnosis according to medical records, specifically with:
Time Frame: up to 12 months
|
|
up to 12 months
|
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
|
up to 12 months
|
|
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
|
|
up to 12 months
|
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
|
|
up to 12 months
|
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
|
|
up to 12 months
|
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
|
|
up to 12 months
|
To describe data on the presence of cardiovascular, neurological and other comorbidities in Russian patients with ATTR PN - Number of patients with concomitant cardiac manifestations, including specifically:
Time Frame: up to 12 months
|
|
up to 12 months
|
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
|
|
up to 12 months
|
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
|
|
up to 12 months
|
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
|
|
up to 12 months
|
Mean and median serum NT-proBNP (pg/ml) concentration
Time Frame: up to 12 months
|
up to 12 months
|
|
Proportion of patients with laboratory confirmed paraproteinemia
Time Frame: up to 12 months
|
up to 12 months
|
|
Mean and median urine albumin-creatinine ratio (UACR, mg/g of creatinine)
Time Frame: up to 12 months
|
up to 12 months
|
|
Proportion of patients with diagnosed CKD, including specifically
Time Frame: up to 12 months
|
|
up to 12 months
|
Number of patients with concomitant renal dysfunction, including specifically
Time Frame: up to 12 months
|
|
up to 12 months
|
Number of patients with confirmed length-dependent peripheral sensory-motor neuropathy based on NCS results
Time Frame: up to 12 months
|
up to 12 months
|
|
Mean and median measured peripheral sensory nerve conduction velocities
Time Frame: up to 12 months
|
|
up to 12 months
|
Number of patients with reduced peripheral sensory nerve conduction velocity at ≥1 site
Time Frame: up to 12 months
|
up to 12 months
|
|
Mean and median measured peripheral motor nerve conduction velocities
Time Frame: up to 12 months
|
|
up to 12 months
|
Number of patients with reduced motor sensory nerve conduction velocity at ≥1 site
Time Frame: up to 12 months
|
up to 12 months
|
|
Mean and median measured sensory action potential (SAP) amplitudes
Time Frame: up to 12 months
|
|
up to 12 months
|
Number of patients with reduced/absent SAP amplitude at ≥1 site
Time Frame: up to 12 months
|
up to 12 months
|
|
Mean and median measured distal compound muscle action potential (dCMAP) amplitudes
Time Frame: up to 12 months
|
|
up to 12 months
|
Mean and median measured proximal compound muscle action potential (pCMAP) amplitudes
Time Frame: up to 12 months
|
|
up to 12 months
|
Number of patients with reduced/absent dCMAP amplitude at ≥1 site
Time Frame: up to 12 months
|
up to 12 months
|
|
Number of patients with reduced/absent pCMAP amplitude at ≥1 site
Time Frame: up to 12 months
|
up to 12 months
|
|
Proportion of patients with each score by each parameter of neurological examination
Time Frame: up to 12 months
|
up to 12 months
|
|
Number of patients in the specific categories of the modified Rankin scale
Time Frame: up to 12 months
|
|
up to 12 months
|
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
|
|
up to 12 months
|
Median number of points according to INCAT upper extremity scale
Time Frame: up to 12 months
|
up to 12 months
|
|
Proportion of patients with specific number of points according to INCAT lower extremity scale
Time Frame: up to 12 months
|
|
up to 12 months
|
Median number of points according to INCAT lower extremity scale
Time Frame: up to 12 months
|
up to 12 months
|
|
Mean and median number of points according to combined clinical and electrophysiological score
Time Frame: up to 12 months
|
up to 12 months
|
|
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
|
|
up to 12 months
|
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
|
|
up to 12 months
|
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:
|
up to 12 months
|
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
|
|
up to 12 months
|
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
|
|
up to 12 months
|
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
|
|
up to 12 months
|
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
|
|
up to 12 months
|
proportion of patients with concomitant renal dysfunction, including specifically
Time Frame: up to 12 months
|
|
up to 12 months
|
proportion of patients with confirmed length-dependent peripheral sensory-motor neuropathy based on NCS results
Time Frame: up to 12 months
|
up to 12 months
|
|
proportion of patients with reduced peripheral sensory nerve conduction velocity at ≥1 site
Time Frame: up to 12 months
|
up to 12 months
|
|
proportion of patients with reduced motor sensory nerve conduction velocity at ≥1 site
Time Frame: up to 12 months
|
up to 12 months
|
|
proportion of patients with reduced/absent SAP amplitude at ≥1 site
Time Frame: up to 12 months
|
up to 12 months
|
|
proportion of patients with reduced/absent dCMAP amplitude at ≥1 site
Time Frame: up to 12 months
|
up to 12 months
|
|
proportion of patients with reduced/absent pCMAP amplitude at ≥1 site
Time Frame: up to 12 months
|
up to 12 months
|
|
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
|
up to 12 months
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Metabolic Diseases
- Nervous System Diseases
- Wounds and Injuries
- Disease
- Genetic Diseases, Inborn
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Mononeuropathies
- Peripheral Nervous System Diseases
- Median Neuropathy
- Nerve Compression Syndromes
- Cumulative Trauma Disorders
- Sprains and Strains
- Proteostasis Deficiencies
- Metabolism, Inborn Errors
- Heredodegenerative Disorders, Nervous System
- Amyloidosis, Familial
- Syndrome
- Carpal Tunnel Syndrome
- Amyloidosis
- Polyneuropathies
- Amyloid Neuropathies
- Amyloid Neuropathies, Familial
Other Study ID Numbers
- D8451R00001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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