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Trial record 26 of 359 for:    transthyretin

Mitochondrial Function in Transthyretin Amyloidosis (MIT-Amylose)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03328338
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : October 24, 2018
Information provided by (Responsible Party):
University Hospital Center of Martinique

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.

Condition or disease
Cardiac Amyloidosis

Detailed Description:

Systemic amyloidosis are a family of diseases induced by misfolded and/or misassembled proteins. Extracellular deposits of these proteins disrupt vital organ function. Two types of amyloid commonly infiltrate the heart: immunoglobulin light-chain amyloid and transthyretin (TTR) amyloid. Among the TTR variants that predominantly target the heart, the valine to isoleucine substitution at position 122 (V122I or Ile122) is the most common. This TTR variant is responsible for the most frequent form of amyloid cardiomyopathy in the Caribbean basin. Increasingly study data supports a central role for circulating or pre-fibrillar amyloidogenic proteins in the disruption of cardiac function in TTR mediated amyloid disease. In vivo exposure of cultured cardiomyocytes to pre-fibrillar an amyloidogenic proteins stimulate the production of reactive oxygen species and disrupts calcium fluxes. (Recent studies indicate that pre-fibrillar amyloidogenic proteins may also induce apoptosis through the mitochondrial pathway, eventually leading to cardiac cell injury). Hence, growing evidence suggests that end-organ damage by pre-fibrillar TTR amyloid may be related to mitochondrial dysfunction. Diagnosis of cardiac amyloidosis can be based on invasive heart biopsies or a non-invasive approach including identification of amyloid tissue deposits from abdominal fat biopsies. The investigators aim is to demonstrate that transthyretin mediated amyloid disease alters the mitochondrial function of subcutaneous abdominal adipocytes.

The investigators objective is to study mitochondrial respiration assessed by oxygraphy in fragments of subcutaneous abdominal fat biopsies performed for diagnosis of TTR amyloidosis. Mitochondrial respiration will be evaluated in the absence and in the presence of ADP.

Follow the evaluation of mitochondrial respiration. So, no patient follow-up will be performed.

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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Mitochondrial Function in Transthyretin Amyloidosis : the MIT-AMYLOSE Study.
Actual Study Start Date : July 17, 2018
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Primary Outcome Measures :
  1. Oxygen consumption measure in subcutaneous abdominal fat biopsies [ Time Frame: Three months ]
    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.

Secondary Outcome Measures :
  1. Rates of oxygen consumption [ Time Frame: Three months ]
    Rates of oxygen consumption (expressed as pmol of fat tissue) will be recorded in-vivo in different conditions, which include routine respiration and after ADP addition. Carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP), tetra methyl-p-phenylenediaminedihydrochloride (TMPD)-ascorbate and oligomycin will be tested in vitro to monitor uncoupled respiration, cytochrome c oxidase activity and leak state respiration by inhibition of ATP synthase, respectively.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03328338

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Contact: Jocelyne CRASPAG, Master (0)596592698 ext +596

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CHU de Martinique Recruiting
Fort-de-France, Martinique, 97261
Contact: Jocelyn INAMO, MD-PhD    (0)596306422 ext +596   
Contact: Rémi NEVIERE, Prof-PhD    (0)596553604 code 1234 ext +596   
Sponsors and Collaborators
University Hospital Center of Martinique
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Principal Investigator: Jocelyn INAMO, MD-PhD CHU de Martinique

Publications of Results:

Other Publications:
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Responsible Party: University Hospital Center of Martinique Identifier: NCT03328338     History of Changes
Other Study ID Numbers: 16/E/17
First Posted: November 1, 2017    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All collected IPD, all IPD that underlie results in a publication.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital Center of Martinique:
Oxidative phosphorylation (mitochondrial respiration)
Subcutaneous abdominal adipose tissue

Additional relevant MeSH terms:
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Amyloid Neuropathies, Familial
Proteostasis Deficiencies
Metabolic Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Amyloid Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Amyloidosis, Familial
Metabolism, Inborn Errors