Sporadic Amyotrophic Lateral SclerosisEarly Phase 1Fibro-ALSNCT02969759
Bioenergetics and Protein Metabolism in Sporadic Amyotrophic Lateral Sclerosis
A Early Phase 1 study testing Skin Biopsy in people with Sporadic Amyotrophic Lateral Sclerosis, run by University Hospital, Angers.
Trial summary
INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disease of the motor neurones of the brain and the spinal cord. The pathophysiological mechanisms of the disease remain unknown. The average age of onset of ALS is about 60 years old, and the mean survival of patients is about 2 years. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Sporadic Amyotrophic Lateral Sclerosis
- What is being tested?
- Skin Biopsy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Nov 2016to Nov 2019
- Phase
- Early Phase 1
- 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 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- a free signed an written consent
- aged between 18 and 80 years old
- ALS defined by El Escorial Criteria
- normal neurological examination
Who cannot join
- comorbidity or treatment susceptible to impact on metabolism
- differential diagnosis suspected, early and late forms (<6 month > 3 years)
- ALS not defined by El Escorial Criteria
- withdrawal of consent to participate
About this study
INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disease of the motor neurones of the brain and the spinal cord. The pathophysiological mechanisms of the disease remain unknown. The average age of onset of ALS is about 60 years old, and the mean survival of patients is about 2 years. The disease is responsible for a progressive paralysis leading to death from respiratory failure. The only treatment available is the Riluzole, with a very modest efficiency on the progression of the disease. ALS is the third neurodegenerative disease, affecting 6000 persons in France, 150 000 in the world. Among the protagonists involved in the occurrence of the disease, mitochondrial perturbations and protein accumulations seem to be central elements.
OBJECTIVES: To precise the implication of energy and protein metabolism in the sporadic forms of ALS, to identify potential biomarkers of the disease and to test new therapies.
Read more
METHODS: The investigators will study cell growth, bioenergetics, mitochondrial dynamics, free-radicals production, presence of cytoplasmic inclusions, cytoskeleton structure and stress response in primary skin fibroblasts obtained from sporadic ALS patients. The study will be conducted over a period of three years in 3 centres specialized respectively in motor neuron diseases, mitochondrial metabolism and neuronal cytoskeleton.
PROSPECTS: If the investigators achieve to identify differences between ALS fibroblasts and controls, the results will be key elements to reinforce the hypothesis of a systemic disease with an important metabolic participation, to better define ALS pathophysiological mechanisms, to find potential biomarkers and to test new therapies.
Read the detailed description
The investigators will study fibroblasts derived from sporadic ALS patients.
Clinical parameters will be collected such as sex, age, age of onset, clinical presentation, electrophysiological an respiratory parameters, treatments.
Patients and controls derived fibroblasts will be amplified and cultivated from skin biopsies.
Primary fibroblast cell cultures will be derived from skin biopsies obtained from control subjects and from the patients after obtaining written consent. Amplifications will be performed, from passage 1 to 6, allowing the time for cell cryopreservation of 10 samples per cell line. All experiments will be conducted on cells with similar passage numbers, ranging from 6 to 25, to avoid artefacts due to senescence.
Cell growth of each line will be monitored with the IncuCyte ZOOM® system (Essen Biosciences), a microscope gantry that resides in a cell incubator, and a networked external controller hard drive that gathers and processes image data. Cell growth will be automatically calculated at each time point using the relative cell density (ratio of the occupied area to the total area of the acquired regions).
The respiratory parameters of the fibroblasts will be monitored precisely with an high resolution oxygraph (OROBOROS). Enzymatic activity of each complex of the mitochondrial respiratory chain will be measured by spectrometry, and the mitochondrial membrane potential will be studied with fluorescence microscopy (TMRM probe). The investigators will also study mitochondrial dynamics and the architecture of mitochondrial network with fluorescence microscopy and super-resolution microscopy (SRM, Roper). The production of free radicals will be estimated with probes sensitive to oxidative stress. Finally, a metabolomic study (mass spectrometry QTRAP LC/MS/MS 5500 ABSciex) will be performed to characterise precisely the metabolites in the cells and to assess their metabolic profile.
The investigators will search for protein inclusions (intermediate filaments, TDP43, FUS, ubiquitin) with immuno-fluorescence technics. Western Blots will be performed to study the protein metabolism. The architecture of the cytoskeleton will be analysed in SRM and fluorescence microscopy, and the investigators will try to transfect fibroblasts in order to express Neurofilaments and study the consequences on the cytoskeleton and protein metabolism.
The investigators will study the response of the cells to the stress (hypoxia SCI-tive Dual, starvation), and to senescence (high passage numbers).
- Conditions
- Sporadic Amyotrophic Lateral Sclerosis
- Being tested
- Skin Biopsy
- Keywords
- Bioenergetics, Protein Metabolism, Sporadic Amyotrophic Lateral Sclerosis
- Medical subject headings
- Amyotrophic lateral sclerosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Skin BiopsyOther
| Study group | Role | What they receive |
|---|---|---|
| Patients | Other | ALS defined by El Escorial Criteria. Receives: Other: Skin Biopsy |
| Controls | Other | Asymptomatic subjects with normal examination. Receives: Other: Skin Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kinetics of fibroblast growth
The growth rates of the fibroblast lines
Measured: 24 hours
Secondary outcomes (3)
Mitochondrial metabolism
the breath parameters of fibroblast will be precisely studied by oxygraphy, a method consisting in measuring the oxygen consumption rates of fibroblasts in different metabolic phases
Measured: 24 hours
Protéic metabolism
The presence of intracytoplasmic inclusion of target protein will be sought.
Measured: 24 hours
stress in senescence answer
the answer due to the stress of cell lines in hypoxia and nutritionnal lack will be studied.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2016 (estimated)
- Study startNov 2016
- Primary completionNov 2017 (estimated)
- Study completionNov 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sporadic Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by University Hospital, AngersThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02969759
- Sponsor's protocol ID
- 2016/36
- Acronym
- Fibro-ALS
- Status last verified
- Nov 2016
- First submitted
- 4 Nov 2016
- Last updated
- 23 Nov 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bioenergetics and Protein Metabolism in Sporadic Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT02969759
- Acronym / sponsor ID
- Fibro-ALS / 2016/36
- Conditions
- Sporadic Amyotrophic Lateral Sclerosis
- Keywords
- Bioenergetics, Protein Metabolism, Sporadic Amyotrophic Lateral Sclerosis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- Nov 2016
- Primary completion
- Nov 2017 (estimated)
- Study completion
- Nov 2019 (estimated)
- First posted
- 21 Nov 2016 (estimated)
- 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.
INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a degenerative disease of the motor neurones of the brain and the spinal cord. The pathophysiological mechanisms of the disease remain unknown. The average age of onset of ALS is about 60 years old, and the mean survival of patients is about 2 years. The disease is responsible for a progressive paralysis leading to death from respiratory failure. The only treatment available is the Riluzole, with a very modest efficiency on the progression of the disease. ALS is the third neurodegenerative disease, affecting 6000 persons in France, 150 000 in the world. Among the protagonists involved in the occurrence of the disease, mitochondrial perturbations and protein accumulations seem to be central elements.
OBJECTIVES: To precise the implication of energy and protein metabolism in the sporadic forms of ALS, to identify potential biomarkers of the disease and to test new therapies.
METHODS: The investigators will study cell growth, bioenergetics, mitochondrial dynamics, free-radicals production, presence of cytoplasmic inclusions, cytoskeleton structure and stress response in primary skin fibroblasts obtained from sporadic ALS patients. The study will be conducted over a period of three years in 3 centres specialized respectively in motor neuron diseases, mitochondrial metabolism and neuronal cytoskeleton.
PROSPECTS: If the investigators achieve to identify differences between ALS fibroblasts and controls, the results will be key elements to reinforce the hypothesis of a systemic disease with an important metabolic participation, to better define ALS pathophysiological mechanisms, to find potential biomarkers and to test new therapies.
Detailed description
The investigators will study fibroblasts derived from sporadic ALS patients.
Clinical parameters will be collected such as sex, age, age of onset, clinical presentation, electrophysiological an respiratory parameters, treatments.
Patients and controls derived fibroblasts will be amplified and cultivated from skin biopsies.
Primary fibroblast cell cultures will be derived from skin biopsies obtained from control subjects and from the patients after obtaining written consent. Amplifications will be performed, from passage 1 to 6, allowing the time for cell cryopreservation of 10 samples per cell line. All experiments will be conducted on cells with similar passage numbers, ranging from 6 to 25, to avoid artefacts due to senescence.
Cell growth of each line will be monitored with the IncuCyte ZOOM® system (Essen Biosciences), a microscope gantry that resides in a cell incubator, and a networked external controller hard drive that gathers and processes image data. Cell growth will be automatically calculated at each time point using the relative cell density (ratio of the occupied area to the total area of the acquired regions).
The respiratory parameters of the fibroblasts will be monitored precisely with an high resolution oxygraph (OROBOROS). Enzymatic activity of each complex of the mitochondrial respiratory chain will be measured by spectrometry, and the mitochondrial membrane potential will be studied with fluorescence microscopy (TMRM probe). The investigators will also study mitochondrial dynamics and the architecture of mitochondrial network with fluorescence microscopy and super-resolution microscopy (SRM, Roper). The production of free radicals will be estimated with probes sensitive to oxidative stress. Finally, a metabolomic study (mass spectrometry QTRAP LC/MS/MS 5500 ABSciex) will be performed to characterise precisely the metabolites in the cells and to assess their metabolic profile.
The investigators will search for protein inclusions (intermediate filaments, TDP43, FUS, ubiquitin) with immuno-fluorescence technics. Western Blots will be performed to study the protein metabolism. The architecture of the cytoskeleton will be analysed in SRM and fluorescence microscopy, and the investigators will try to transfect fibroblasts in order to express Neurofilaments and study the consequences on the cytoskeleton and protein metabolism.
The investigators will study the response of the cells to the stress (hypoxia SCI-tive Dual, starvation), and to senescence (high passage numbers).
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | Other | Other: Skin BiopsyALS defined by El Escorial Criteria. |
| Controls | Other | Other: Skin BiopsyAsymptomatic subjects with normal examination. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- a free signed an written consent
- aged between 18 and 80 years old
- ALS defined by El Escorial Criteria
- normal neurological examination
Key exclusion criteria (4 listed)
- comorbidity or treatment susceptible to impact on metabolism
- differential diagnosis suspected, early and late forms (<6 month > 3 years)
- ALS not defined by El Escorial Criteria
- withdrawal of consent to participate
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Skin Biopsy | Other | Controls, Patients |
Primary outcome
Kinetics of fibroblast growth
Time frame: 24 hours
The growth rates of the fibroblast lines
3 secondary outcomes
Mitochondrial metabolism
Time frame: 24 hours
Protéic metabolism
Time frame: 24 hours
stress in senescence answer
Time frame: 24 hours
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2016.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Skin Biopsy in people with Sporadic Amyotrophic Lateral Sclerosis, run by University Hospital, Angers.
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 4 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 23 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
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?
Kinetics of fibroblast growth (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Nov 2016.