Mitochondrial Function in Transthyretin Amyloidosis

NCT03328338 | Terminated

• 1 other identifier: 16/E/17
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Hereditary (familial) amyloidosis arising from the misfolding of a mutated or variant transthyretin, is the most frequent form of amyloid cardiomyopathy in the Caribbean basin. Affected organs invariably harbor extracellular amyloid deposits in the myocardium. Circulating or pre-fibrillar amyloidogenic proteins are implicated in the disruption of cell function. The investigators aim is to demonstrate that transthyretin mediated amyloid disease alter the mitochondrial function of cardiac cells.

Conditions

Cardiac Amyloidosis

Keywords

Mitochondria; Oxidative phosphorylation (mitochondrial respiration); Subcutaneous abdominal adipose tissue; Heart.

Outcome Measures

Primary Outcomes (1)

• Oxygen consumption measure in subcutaneous abdominal fat biopsies

  The mitochondrial respiration of the cells is measured by polarography with a "Clark" type oxygen electrode. The Clark electrode consists of a platinium cathode and a silver anode. When a potential difference of -0.6 volts is applied, the platinium electrode is negatively charged with respect to that of silver and each oxygen molecule dissolved in the medium diffuses through the gas-permeable Teflon membrane, and is reduced at the cathode according to the following reaction: O 2 + 4H + + 4e → 2H 2 O. The current thus generated is proportional to the concentration of dissolved oxygen. The oxygen saturation constant (406 nmol / ml) makes it possible to convert these results into oxygen consumption / minute.

  Three months

Secondary Outcomes (1)

• Rates of oxygen consumption

  Three months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The selection of patients is done during the amyloidosis consultation of the cardiology department. Patients are referred to this consultation following the discovery of characteristic abnormalities during echocardiography.

You may qualify if:

• Have a parietal thickness measuring more than 15 mm on the echocardiography or have structural and echogenicity abnormalities characteristic of cardiac amyloidosis,
• Live in Martinique,
• Accept the use of the residues coming from biopsies of the subcutaneous abdominal adipose tissue performed during the medical care.

You may not qualify if:

• Be under 18 years old,
• Have a contraindication to subcutaneous biopsy,
• Be allergic to local anesthetics,
• Pregnant or nursing woman,
• Have a cardiovascular disease suggesting a secondary cardiac disease, such as documented severe hypertension, valvular stenosis, or a known familial cardiomyopathy,
• Be major under guardianship / curatorship or deprived of liberty,
• Not be able to answer to a simple administrative questionnaire or to give freely its non-opposition.

Sponsors & Collaborators

• University Hospital Center of Martinique: lead

Study Sites (1)

CHU de Martinique

Fort-de-France, 97261, Martinique

Location

Related Publications (6)

• Inamo J, Daigre JL, Boissin JL, Kangambega P, Larifla L, Chevallier H, Balkau B, Smadja D, Atallah A. High blood pressure and obesity: disparities among four French Overseas Territories. J Hypertens. 2011 Aug;29(8):1494-501. doi: 10.1097/HJH.0b013e328348fd95.

  PMID: 21720269 BACKGROUND

• Oliveira Da Silva L, Fabre J, Monfort A, Villeret J, Citony I, Cohen-Tenoudji P, Lebbadi M, Martin D, Molinie V, Inamo J. 'Green Apple' Heart Failure. West Indian Med J. 2014 Jul 3;63(6):673-5. doi: 10.7727/wimj.2013.255. Epub 2014 Jun 25.

  PMID: 25803389 RESULT

• Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, Habibi A, Bennani S, Savale L, Adnot S, Maitre B, Yaici A, Hajji L, O'Callaghan DS, Clerson P, Girot R, Galacteros F, Simonneau G. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011 Jul 7;365(1):44-53. doi: 10.1056/NEJMoa1005565.

  PMID: 21732836 RESULT

• Montaigne D, Marechal X, Coisne A, Debry N, Modine T, Fayad G, Potelle C, El Arid JM, Mouton S, Sebti Y, Duez H, Preau S, Remy-Jouet I, Zerimech F, Koussa M, Richard V, Neviere R, Edme JL, Lefebvre P, Staels B. Myocardial contractile dysfunction is associated with impaired mitochondrial function and dynamics in type 2 diabetic but not in obese patients. Circulation. 2014 Aug 12;130(7):554-64. doi: 10.1161/CIRCULATIONAHA.113.008476. Epub 2014 Jun 13.

  PMID: 24928681 RESULT

• Montaigne D, Marechal X, Lefebvre P, Modine T, Fayad G, Dehondt H, Hurt C, Coisne A, Koussa M, Remy-Jouet I, Zerimech F, Boulanger E, Lacroix D, Staels B, Neviere R. Mitochondrial dysfunction as an arrhythmogenic substrate: a translational proof-of-concept study in patients with metabolic syndrome in whom post-operative atrial fibrillation develops. J Am Coll Cardiol. 2013 Oct 15;62(16):1466-73. doi: 10.1016/j.jacc.2013.03.061. Epub 2013 May 1.

  PMID: 23644086 RESULT

• Preau S, Montaigne D, Modine T, Fayad G, Koussa M, Tardivel M, Durocher A, Saulnier F, Marechal X, Neviere R. Macrophage migration inhibitory factor induces contractile and mitochondria dysfunction by altering cytoskeleton network in the human heart. Crit Care Med. 2013 Jul;41(7):e125-33. doi: 10.1097/CCM.0b013e31827c0d8c.

  PMID: 23478658 RESULT

MeSH Terms

Conditions

Amyloid Neuropathies, Familial

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies

Study Officials

• Jocelyn INAMO, MD-PhD

  CHU de Martinique

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2017
• First Posted: November 1, 2017
• Study Start: July 17, 2018
• Primary Completion: September 30, 2019
• Study Completion: December 29, 2019
• Last Updated: August 28, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After the main publication of the results, for not limited time.
• Access Criteria: The conditions for the transfer of all or part of the database of the research are decided by the investigator coordinator / sponsor of the research and are the subject of a written contract.

Locations

MA (1)