Mitochondrial Function in Transthyretin Amyloidosis (MIT-Amylose)
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|ClinicalTrials.gov Identifier: NCT03328338|
Recruitment Status : Recruiting
First Posted : November 1, 2017
Last Update Posted : October 24, 2018
|Condition or disease|
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.
|Study Type :||Observational|
|Estimated Enrollment :||30 participants|
|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|
- 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.
- Rates of oxygen consumption [ Time Frame: Three months ]Rates of oxygen consumption (expressed as pmol O2.s-1.mg 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.
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 ClinicalTrials.gov identifier (NCT number): NCT03328338
|Contact: Jocelyne CRASPAG, Master||(0)596592698 ext +email@example.com|
|CHU de Martinique||Recruiting|
|Fort-de-France, Martinique, 97261|
|Contact: Jocelyn INAMO, MD-PhD (0)596306422 ext +596 firstname.lastname@example.org|
|Contact: Rémi NEVIERE, Prof-PhD (0)596553604 code 1234 ext +596 email@example.com|
|Principal Investigator:||Jocelyn INAMO, MD-PhD||CHU de Martinique|