Observing hereditary transthyretin amyloidosis in patients with carpal tunnel syndrome in Russia

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

This study is trying to see how common a genetic condition called hereditary transthyretin amyloidosis is in people with carpal tunnel syndrome in Russia, using medical records and genetic testing to improve diagnosis and treatment.

Quick facts

• Study type: Observational
• Enrollment: 800 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AstraZeneca (Industry-sponsored)
• Locations: 8 sites (Irkutsk and 7 other locations)
• Trial ID: NCT06414746 on ClinicalTrials.gov

What this trial studies

This multicenter observational study aims to assess the prevalence of hereditary transthyretin amyloidosis polyneuropathy (ATTR PN) in patients diagnosed with carpal tunnel syndrome (CTS) across various locations in Russia. The study includes both retrospective data collection from medical records and prospective phases involving molecular genetic testing. By identifying clinical characteristics and medical needs of these patients, the study seeks to improve early diagnosis and treatment outcomes for ATTR PN, which can often be misdiagnosed. The introduction of genetic testing into routine practice is expected to enhance the reliability of epidemiological data regarding ATTR PN prevalence.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a confirmed diagnosis of carpal tunnel syndrome and specific clinical features indicating potential hereditary ATTR PN.

Not a fit: Patients without a diagnosis of carpal tunnel syndrome or those who do not exhibit the specified clinical features may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to earlier diagnosis and improved treatment options for patients with hereditary transthyretin amyloidosis.

How similar studies have performed: While there have been no prior observational studies on the epidemiology of ATTR PN in the Russian population, similar approaches in other regions have shown promise in identifying and managing hereditary conditions.

Eligibility criteria

Inclusion Criteria:

for the retrospective phase are:

1. Patients with the established diagnosis of CTS.
2. 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).
3. Age ≥ 18 years at the time of CTS diagnosis.
4. Provided written informed consent for the prospective phase of the study (including molecular genetic testing).
5. 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
6. Absence of previously established ATTR PN diagnosis (ICD-10 code Е85.1, "Neuropathic hereditary familial amyloidosis").

Exclusion Criteria:

1. 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:
2. Previously performed TTR genetic testing;
3. Verified B12 deficiency;
4. History of alcohol abuse according to the patient's medical record.

Where this trial is running

Irkutsk and 7 other locations

• Research Site — Irkutsk, Russian Federation (Recruiting)
• Research Site — Kazan, Russian Federation (Recruiting)
• Research Site — Krasnodar, Russian Federation (Recruiting)
• Research Site — Makhachkala, Russian Federation (Recruiting)
• Research Site — Moscow, Russian Federation (Recruiting)
• Research Site — Nizhny Novgorod, Russian Federation (Recruiting)
• Research Site — Samara, Russian Federation (Recruiting)
• Research Site — Yekaterinburg, Russian Federation (Recruiting)

Study contacts

• Study coordinator: AstraZeneca Clinical Study Information Center

Conditions Hereditary Transthyretin Amyloidosis; Carpal Tunnel Syndrome; Polyneuropathy; Amyloidosis; ATTR PN; CTS; PN; carpal tunnel syndrome