A Multicenter Observational retrosPective Registry of patIents With Transthyretin aMyloid polynEuropathy (hATTR-PN) and chRonic Idiopathic Axonal Polyneuropathy (CIAP) in the Population of the Russian Federation
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- In order to describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, Mean age at the hATTR-PN or CIAP diagnosis information will be collected
Study Overview
Brief Summary
A multicenter observational retrosPective Registry of patIents with transthyretin aMyloid polynEuropathy (hATTR-PN) and chRonic idiopathic axonal polyneuropathy (CIAP) in the population of the Russian Federation (PRIMER) There are no comprehensive epidemiological data on patients with hereditary ATTR-PN (hATTR-PN) and CIAP in the Russian Federation. Therefore, there is a need to conduct a large-scale observational study in the Russian population to obtain information on clinical, electrophysiological and demographic characteristics of patients with hATTR-PN and CIAP. Obtaining the study data will help to identify the patients with axonal polyneuropathy, who deserve TTR gene sequencing, and therefore to allow early treatment and potentially modify disease progression in patients.
Detailed Description
Since the increasing number of treatments available to help slow the progression of neuropathy it is critical to timely identify and diagnose the ATTR-PN. Early identification and intervention are also crucial to improve patient outcomes because newly available treatments have been shown to have maximum therapeutic benefit when started in the early stages of the disease.
Identification of ATTRv amyloidosis with PN can be challenging, particularly in non-endemic regions, and a high level of suspicion is required to diagnose patients as early as possible.
Previously proposed suspicion index of ATTRv amyloidosis was based on disease's red flags, that is, on the presence of a progressive polyneuropathy in addition to at least one red flag symptom suggestive of multi-systemic involvement. However, sometimes the demonstration of a progressive neuropathy requires follow-up evaluations, risking wasting time. Moreover, some red flags (e.g., cardiomyopathy or vitreous opacities) need specialist evaluations that could be often lacking during the first neurological evaluation.
Patients can present with heterogeneous symptoms and variable levels of disease severity, which often leads to a misdiagnosis. Early and accurate diagnosis may also be confounded by a lack of family history and the presence of various phenotypes common to multiple disease conditions such as GI disorders. In fact, CIAP still represents a common misdiagnosis for ATTRv patients.
Study is planned to determine the principal differences between the hATTR-PN and CIAP patients and valorize them in a compound score which can help clinician through a specific cut-off to recognize patients deserving TTR genetic analysis. The application of the compound score in patients with sensory-motor neuropathy may have a major role, representing a screening tool to avoiding wasting time and therefore shortening the time to reach a correct diagnosis.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Retrospective
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with hATTR-PN or CIAP ;
- •The diagnosis of hATTR-PN or CIAP was established between the 1st January 2017 and the 1st March 2024;
- •Presence of at least 1 month between the date of hATTR-PN or CIAP diagnosis and the date of inclusion;
- •Age ≥ 18 years at the time of hATTR-PN or CIAP diagnosis.
Exclusion Criteria
- •The participation in any clinical trial with investigational product from the moment of diagnosis of ATTR PN or CIAP until the end of retrospective follow-up period.
Outcomes
Primary Outcomes
In order to describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, Mean age at the hATTR-PN or CIAP diagnosis information will be collected
Time Frame: up to 5 months
In order to describe the baseline demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information on Proportion of women and men will be collected
Time Frame: up to 5 months
In order to describe the baseline demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information on Proportion of patients with each race and ethnicity will be collected
Time Frame: up to 5 months
to describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIA, information on Proportion of patients from each federal district of the Russian Federation will be collected
Time Frame: up to 5 months
In order to describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, Proportion of patients with underweight will be collected
Time Frame: up to 5 months
BMI \<18,5 kg/m2
in order to describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information on Proportion of patients with negative lifestyle factors will be collected:
Time Frame: up to 5 months
1. Proportion of patients with a history of smoking; 2. Proportion of patients with a history of alcohol abuse
To describe the baseline electrophysiological and clinical characteristics of patients, Proportion of patients with chronic sensory or sensorimotor polyneuropathy and progressive chronic polyneuropathy among patients with CIAP will be calculated
Time Frame: up to 5 months
in order to describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, tha following Anthropometric characteristics will be collected:
Time Frame: up to 5 months
Mean height (in m and cm), body weight (in kg), BMI (kg/m2)
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, Proportion of patients with each PND score will be calculated
Time Frame: up to 5 months
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information Mean wall thickness of the left ventricular (LV) will be collected
Time Frame: up to 5 months
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information on Mean NT-proBNP level will be collected
Time Frame: up to 5 months
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information Mean estimated glomerular filtration rate (eGFR) will be collected
Time Frame: up to 5 months
based on CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, Proportion of patients underwent surgery for CTS to the moment of diagnosis will be calculated
Time Frame: up to 5 months
in order to describe the baseline demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information on Proportion of patients with positive family history in close relatives will be collected
Time Frame: up to 5 months
to describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP, information on Mean (or median) time from the first symptoms of neuropathy to the diagnosis of PN will be collected
Time Frame: up to 5 months
to describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP, Proportion of patients with different firstly suspected etiology of PN will be calculated
Time Frame: up to 5 months
1. Diabetic; 2. Alcoholic; 3. Toxic (toxic agents other than alcohol, e.g. drugs or chemotherapy); 4. Other Hereditary; 5. Deficiency (due to vitamin B12, thiamine or pyridoxine deficiency); 6. Immunological (due to rheumatological, paraneoplastic or celiac disease); 7. Haematological (paraproteinemic syndromes); 8. Infective; 9. Idiopathic; 10. Other;
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, Proportion of patients with each score by each parameter of neurological examination will be calculated
Time Frame: up to 5 months
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information on Mean left ventricular ejection fraction (LVEF) will be collected
Time Frame: up to 5 months
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, Proportion of patients with a positive paraprotein blood test result will be calculated
Time Frame: up to 5 months
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP, information on Mean (or median) time from first PN manifestation/diagnosis to the hATTR-PN or CIAP diagnosis will be collected
Time Frame: up to 5 months
To describe the baseline clinical characteristics of patients with hATTR-PN and CIAP, Proportion of patients with each result of TTR gene testing will be calculated
Time Frame: up to 5 months
(positive, negative, not performed); the proportion of patients with each identified mutation in TTR gene in case of positive result
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information on Mean blood pressure (BP) (systolic and diastolic) and Mean heart rate (HR)
Time Frame: up to 5 months
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, Proportion of patients with each clinical manifestation will be calculated:
Time Frame: up to 5 months
1. Sensory symptoms; 2. Motor symptoms; 3. CTS (proportion of patients with any CTS in total, as well as proportion of patients with uni- and bilateral CTS); 4. Biceps tendon rupture; 5. Autonomic symptoms; 6. Spinal channel stenosis of the lumbar region; 7. GI symptoms; 8. Ocular manifestations; 9. Cardiac manifestations; 10. Renal manifestations; 11. CNS involvement.
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information on Mean point by MRS will be calculated
Time Frame: up to 5 months
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information on Mean point by INCAT scale (total score, arm disability, leg disability) will be collected
Time Frame: up to 5 months
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, Proportion of patients with diagnosis of HFpEF will be calculated
Time Frame: up to 5 months
To describe the baseline electrophysiological characteristics of patients with hATTR-PN and CIAP, information Mean variables based on the results of electrophysiological investigation, including the following (on both extremities) will be collected
Time Frame: up to 5 months
Compound muscular action potential (CMAP) (mV) of the median, ulnar, tibial and peroneal nerves; (b) (Distal motor latency) DML (ms) of the median, ulnar, tibial and peroneal nerves; (c) (Motor nerve conduction velocity) MNCV (m/s) of the median, ulnar, tibial and peroneal nerves; (d) Sensory action potential (SAP) (μV) of the median, ulnar, peroneal superficial and sural nerves; (e) Sensory nerve conduction velocity (SNCV) (m/s) of the median, ulnar, peroneal superficial and sural nerves
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, information on Mean urine albumin-to-creatinine ratio (UACR) in a spot urine sample will be collected
Time Frame: up to 5 months
To describe the baseline electrophysiological, clinical and demographic characteristics of patients with hATTR-PN and CIAP in the Russian Federation, Proportion of patients with each concomitant disease will be calculated
Time Frame: up to 5 months
Secondary Outcomes
- To arrange a score to select patients with axonal neuropathy who deserve screening for TTR mutation.(Up to 5 months)