Cardiac AmyloidosisMIT-AmyloseNCT03328338
Mitochondrial Function in Transthyretin Amyloidosis
An observational study of Cardiac Amyloidosis, run by University Hospital Center of Martinique at 1 site in Martinique.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Amyloidosis
- How many people
- 12 participants
- Where
- 1 siteMartinique
- Study dates
- 17 Jul 2018to 29 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mitochondrial Function in Transthyretin Amyloidosis : the MIT-AMYLOSE Study.
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.
Read the 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.
- Conditions
- Cardiac Amyloidosis
- Keywords
- Mitochondria, Oxidative phosphorylation (mitochondrial respiration), Subcutaneous abdominal adipose tissue, Heart.
- Medical subject headings
- Amyloid Neuropathies, Familial
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Three months
Secondary outcomes (1)
Rates of oxygen consumption
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.
Measured: Three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2017
- Study start17 Jul 2018
- Primary completion30 Sep 2019
- Study completion29 Dec 2019
Why it stopped: Mitochondrial respiration measurement technique faulty
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Cardiac AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Center of Martinique
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jocelyn INAMO, MD-PhD, Principal investigator, CHU de Martinique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03328338
- Sponsor's protocol ID
- 16/E/17
- Acronym
- MIT-Amylose
- Status last verified
- Aug 2023
- First submitted
- 28 Oct 2017
- Last updated
- 28 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All collected IPD, all IPD that underlie results in a publication.
Publications
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.
PubMed 21720269Oliveira 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.
PubMed 25803389Parent 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.
PubMed 21732836Montaigne 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.
PubMed 24928681Montaigne 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.
PubMed 23644086Preau 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.
PubMed 23478658
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mitochondrial Function in Transthyretin Amyloidosis : the MIT-AMYLOSE Study.
- ClinicalTrials.gov ID
- NCT03328338
- Acronym / sponsor ID
- MIT-Amylose / 16/E/17
- Conditions
- Cardiac Amyloidosis
- Keywords
- Mitochondria, Oxidative phosphorylation (mitochondrial respiration), Subcutaneous abdominal adipose tissue, Heart.
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Mitochondrial respiration measurement technique faulty
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Hospital Center of MartiniqueUniversity, hospital or other
- Study start
- 17 Jul 2018 (actual)
- Primary completion
- 30 Sep 2019 (actual)
- Study completion
- 29 Dec 2019 (actual)
- First posted
- 1 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
1 secondary outcome
Rates of oxygen consumption
Time frame: Three months
Results and safety
The study was stopped early (reason given: Mitochondrial respiration measurement technique faulty). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2023.
- Background: PubMed 21720269Inamo 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.
- Results publication: PubMed 25803389Oliveira 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.
- Results publication: PubMed 21732836Parent 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.
- Results publication: PubMed 24928681Montaigne 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.
- Results publication: PubMed 23644086Montaigne 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.
- Results publication: PubMed 23478658Preau 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.
- Individual participant dataSharing planned: Yes. All collected IPD, all IPD that underlie results in a publication.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jocelyn INAMO, MD-PhD principal investigator
CHU de Martinique
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiac Amyloidosis, run by University Hospital Center of Martinique at 1 site in Martinique.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Martinique. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Mitochondrial respiration measurement technique faulty). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oxygen consumption measure in subcutaneous abdominal fat biopsies (time frame: Three months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03328338, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2023.