Parametric Cardiac 18F-flutemetamol PET Imaging in ATTR Cardiomyopathy

Cardiomyopathies, Primary Clinical Trial

Official title:

Parametric Cardiac 18F-flutemetamol PET Imaging in ATTR Cardiomyopathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05374564
• Other study ID #: 2000031407
• Status: Recruiting
• Phase: Phase 1
• Start date: August 16, 2022
• Est. completion date: June 2025

Study information

• Verified date: June 2024
• Source: Yale University
• Contact: Maxime Oriol, BS
• Phone: 2037856497
• Email: maxime.oriol[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

18F-Flutemetamol (Vizamyl) is a radioactive diagnostic agent indicated and FDA-approved for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD) or other causes of cognitive decline. This study is designed to evaluate a novel use for 18F-Flutemetamol in cardiac amyloidosis.

Description:

The goal of this project is to perform a proof-of-concept study to compare the ability of quantitative parametric cardiac 18F-flutemetamol positron emission tomography (PET) to assess baseline and change in disease burden after six months of therapy with tafamidis treatment in 12 patients diagnosed with transthyretin cardiac amyloidosis (ATTR-CA) at Yale-New Haven Hospital. The primary outcome of the study will be comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET metrics between the baseline and six-month 18F-flutemetamol PET scans versus clinical stage and echocardiographic features (wall thickness, strain, LVEF).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. Age > 18 years
• 2. Diagnosis of ATTR cardiac amyloidosis (wild-type or V142I ATTR mutation) a. Diagnosis of ATTR cardiac amyloidosis by established consensus diagnostic criteria of Gillmore et al. (either invasive or non-invasive diagnostic pathways)
• 3. Plan for initiation of tafamidis therapy for clinical indications and agree to continue tafamidis during the duration of the study.
• 4. Stated willingness to comply with all study procedures and availability for the duration of the study
• 5. Able to understand and sign the informed consent document after the nature of the study has been fully explained.
• 6. Women of childbearing potential who are sexually active with a non-sterilized male partner and males who are sexually active with a partner of childbearing potential must agree to use adequate contraception from screening until 30 days after the Flutemetamol.

Exclusion Criteria:

• 1. Primary amyloidosis (AL) or secondary amyloidosis (AA).
• 2. Prior liver or heart transplantation.
• 3. Active malignancy or non-amyloid disease with an expected survival of less than 1 year
• 4. Inability to lie flat for 60 minutes in the PET scanner
• 5. History of prior treatment for ATTR cardiomyopathy and/or amyloid neuropathy, or decline clinical tafamidis treatment.
• 6. Pregnancy or lactation
• 7. Known allergic reactions to components of the 18F-flutemetamol and/or polysorbate 80
• 8. High risk for non-adherence as determined by screening evaluation.

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathies, Primary

Intervention

Drug:
• (18F)Flutemetamol
18F-Flutemetamol binds to ß-amyloid plaques and the F-18 isotope produces a positron signal that is detected by a PET scanner. Multiple recent studies have shown that thioflavin-analogue tracers such as 18F-flutemetamol may be able to fulfill the unmet need of elucidating the presence of amyloid deposition in the heart. Because it binds to the beta-pleated motif of the amyloid fibril due to their similarity to the thioflavin structure, 18F-Flutemetamol could potentially be used to image cardiac amyloidosis (CA)

Locations

Country	Name	City	State
United States	Yale University	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (26)

Buxbaum J, Jacobson DR, Tagoe C, Alexander A, Kitzman DW, Greenberg B, Thaneemit-Chen S, Lavori P. Transthyretin V122I in African Americans with congestive heart failure. J Am Coll Cardiol. 2006 Apr 18;47(8):1724-5. doi: 10.1016/j.jacc.2006.01.042. Epub 2 — View Citation

Castano A, Narotsky DL, Hamid N, Khalique OK, Morgenstern R, DeLuca A, Rubin J, Chiuzan C, Nazif T, Vahl T, George I, Kodali S, Leon MB, Hahn R, Bokhari S, Maurer MS. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients wi — View Citation

Choi Y, Hawkins RA, Huang SC, Brunken RC, Hoh CK, Messa C, Nitzsche EU, Phelps ME, Schelbert HR. Evaluation of the effect of glucose ingestion and kinetic model configurations of FDG in the normal liver. J Nucl Med. 1994 May;35(5):818-23. — View Citation

Damy T, Kristen AV, Suhr OB, Maurer MS, Plante-Bordeneuve V, Yu CR, Ong ML, Coelho T, Rapezzi C; THAOS Investigators. Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amyloidosis Outcomes Survey (THAOS) — View Citation

Delforge J, Syrota A, Mazoyer BM. Identifiability analysis and parameter identification of an in vivo ligand-receptor model from PET data. IEEE Trans Biomed Eng. 1990 Jul;37(7):653-61. doi: 10.1109/10.55673. — View Citation

Dietemann S, Nkoulou R. Amyloid PET imaging in cardiac amyloidosis: a pilot study using 18F-flutemetamol positron emission tomography. Ann Nucl Med. 2019 Aug;33(8):624-628. doi: 10.1007/s12149-019-01372-7. Epub 2019 May 28. — View Citation

Donnelly JP, Hanna M, Sperry BW, Seitz WH Jr. Carpal Tunnel Syndrome: A Potential Early, Red-Flag Sign of Amyloidosis. J Hand Surg Am. 2019 Oct;44(10):868-876. doi: 10.1016/j.jhsa.2019.06.016. Epub 2019 Aug 7. — View Citation

Feher A, Srivastava A, Quail MA, Boutagy NE, Khanna P, Wilson L, Miller EJ, Liu YH, Lee F, Sinusas AJ. Serial Assessment of Coronary Flow Reserve by Rubidium-82 Positron Emission Tomography Predicts Mortality in Heart Transplant Recipients. JACC Cardiovas — View Citation

Gallegos C, Miller EJ. Advances in PET-Based Cardiac Amyloid Radiotracers. Curr Cardiol Rep. 2020 May 19;22(6):40. doi: 10.1007/s11886-020-01284-3. — View Citation

Gillmore JD, Damy T, Fontana M, Hutchinson M, Lachmann HJ, Martinez-Naharro A, Quarta CC, Rezk T, Whelan CJ, Gonzalez-Lopez E, Lane T, Gilbertson JA, Rowczenio D, Petrie A, Hawkins PN. A new staging system for cardiac transthyretin amyloidosis. Eur Heart — View Citation

Gonzalez-Lopez E, Gallego-Delgado M, Guzzo-Merello G, de Haro-Del Moral FJ, Cobo-Marcos M, Robles C, Bornstein B, Salas C, Lara-Pezzi E, Alonso-Pulpon L, Garcia-Pavia P. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejecti — View Citation

Gunn RN, Gunn SR, Cunningham VJ. Positron emission tomography compartmental models. J Cereb Blood Flow Metab. 2001 Jun;21(6):635-52. doi: 10.1097/00004647-200106000-00002. — View Citation

Heurling K, Buckley C, Van Laere K, Vandenberghe R, Lubberink M. Parametric imaging and quantitative analysis of the PET amyloid ligand [(18)F]flutemetamol. Neuroimage. 2015 Nov 1;121:184-92. doi: 10.1016/j.neuroimage.2015.07.037. Epub 2015 Jul 22. — View Citation

Jacobson DR, Alexander AA, Tagoe C, Garvey WT, Williams SM, Tishkoff S, Modiano D, Sirima SB, Kalidi I, Toure A, Buxbaum JN. The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa. Mol Genet Genomic Med. 2016 Jul 1 — View Citation

Kazi DS, Bellows BK, Baron SJ, Shen C, Cohen DJ, Spertus JA, Yeh RW, Arnold SV, Sperry BW, Maurer MS, Shah SJ. Cost-Effectiveness of Tafamidis Therapy for Transthyretin Amyloid Cardiomyopathy. Circulation. 2020 Apr 14;141(15):1214-1224. doi: 10.1161/CIRCU — View Citation

Leuzy A, Savitcheva I, Chiotis K, Lilja J, Andersen P, Bogdanovic N, Jelic V, Nordberg A. Clinical impact of [18F]flutemetamol PET among memory clinic patients with an unclear diagnosis. Eur J Nucl Med Mol Imaging. 2019 Jun;46(6):1276-1286. doi: 10.1007/s — View Citation

Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL. Distribution volume ratios without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab. 1996 Sep;16(5):834-40. doi: 10.1097/00004647-199609000-00008. — View Citation

Masri A, Chen H, Wong C, Fischer KL, Karam C, Gellad WF, Heitner SB. Initial Experience Prescribing Commercial Tafamidis, the Most Expensive Cardiac Medication in History. JAMA Cardiol. 2020 Sep 1;5(9):1066-1067. doi: 10.1001/jamacardio.2020.1738. — View Citation

Maurer MS, Bokhari S, Damy T, Dorbala S, Drachman BM, Fontana M, Grogan M, Kristen AV, Lousada I, Nativi-Nicolau J, Cristina Quarta C, Rapezzi C, Ruberg FL, Witteles R, Merlini G. Expert Consensus Recommendations for the Suspicion and Diagnosis of Transth — 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; — View Citation

Mockelind S, Axelsson J, Pilebro B, Lindqvist P, Suhr OB, Sundstrom T. Quantification of cardiac amyloid with [18F]Flutemetamol in patients with V30M hereditary transthyretin amyloidosis. Amyloid. 2020 Sep;27(3):191-199. doi: 10.1080/13506129.2020.1760237 — View Citation

Papathanasiou M, Kessler L, Carpinteiro A, Hagenacker T, Nensa F, Umutlu L, Forsting M, Brainman A, Kleinschnitz C, Antoch G, Duhrsen U, Schlosser TW, Herrmann K, Rassaf T, Luedike P, Rischpler C. 18F-flutemetamol positron emission tomography in cardiac a — View Citation

Papoutsidakis N, Miller EJ, Rodonski A, Jacoby D. Time Course of Common Clinical Manifestations in Patients with Transthyretin Cardiac Amyloidosis: Delay From Symptom Onset to Diagnosis. J Card Fail. 2018 Feb;24(2):131-133. doi: 10.1016/j.cardfail.2017.12 — View Citation

Quarta CC, Buxbaum JN, Shah AM, Falk RH, Claggett B, Kitzman DW, Mosley TH, Butler KR, Boerwinkle E, Solomon SD. The amyloidogenic V122I transthyretin variant in elderly black Americans. N Engl J Med. 2015 Jan 1;372(1):21-9. doi: 10.1056/NEJMoa1404852. — View Citation

Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, Singleton A, Kiuru-Enari S, Paetau A, Tienari PJ, Myllykangas L. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobuli — View Citation

Ye Q, Wu J, Lu Y, Naganawa M, Gallezot JD, Ma T, Liu Y, Tanoue L, Detterbeck F, Blasberg J, Chen MK, Casey M, Carson RE, Liu C. Improved discrimination between benign and malignant LDCT screening-detected lung nodules with dynamic over static 18F-FDG PET — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol	As determined by comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET visual uptake scores between the baseline and six-month PET scans	6 months
Primary	Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol	As determined by comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET percent maximal counts between the baseline and six-month PET scans	6 months
Primary	Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol	As determined by comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET Standardized Uptake Values (SUVs) between the baseline and six-month PET scans	6 months
Primary	Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol	As determined by comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET retention index between the baseline and six-month PET scans	6 months
Primary	Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol	As determined by comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET Vt between the baseline and six-month PET scans	6 months
Primary	Determine if treatment with tafamidis reduces 18F-flutemetamol cardiac PET imaging markers	As assessed by dynamic cardiac PET between baseline and 6 months	6 months
Secondary	Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response	As determined by ATTR clinical stage baseline and following 6 months of treatment with tafamidis.	6 months
Secondary	Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response	As determined by NT-proBNP between baseline and following 6 months of treatment with tafamidis.	6 months
Secondary	Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response	As determined by TnT between baseline and following 6 months of treatment with tafamidis.	6 months
Secondary	Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response	As determined by echocardiographic wall thickness between baseline and following 6 months of treatment with tafamidis.	6 months
Secondary	Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response	As determined by global longitudinal strain between baseline and following 6 months of treatment with tafamidis.	6 months