Brain Neuroimaging Biomarkers in Huntington DiseaseHDeNERGYNCT02639871
Dynamic Neuroimaging Biomarkers in Huntington's Disease
An observational study of Brain Neuroimaging Biomarkers in Huntington Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
There is no curative treatment available today in Huntington disease (HD) despite the identification of the mutated gene 20 years ago. Nonetheless, safe and promising therapeutic strategies targeting brain energy metabolism are now becoming available. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Brain Neuroimaging Biomarkers in Huntington Disease
- How many people
- 81 participants
- Where
- 1 siteFrance
- Study dates
- 28 Jun 2016to 24 Jun 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Period 1: healthy volunteers; Period 2: presymptomatic individuals, early affected HD patients and controls
Who may be able to join
- Healthy Volunteers Period 1:
- At least 18 years of age
- Signature of the informed consent
- Covered by social security
- Participants Period 2:
- At least 18 years of age
Show all 32Show fewer
- Signature of the informed consent
- Covered by social security
- Presymptomatic individuals: Positive genetic test with CAG repeat length > 39 in HTT gene, UHDRS score < 5
- Early affected patients: Positive genetic test with CAG repeat length > 39 in HTT gene and UHDRS score between 5 and 40
- BMI between 18 and 30
- Non-inclusion criteria
- Healthy Volunteers Period 1:
- Contra-indications to MRI (claustrophobia, metallic or material implants)
- History of severe head injury
- Participation in another trial
- Pregnancy and breastfeeding
- Inability to understand information about the protocol
- Persons deprived of their liberty by judicial or administrative decision
- Adult subject under legal protection or unable to consent.
- Unwillingness to be informed in case of abnormal MRI
- Participants Period 2:
- Contra-indications to MRI (claustrophobia, metallic or material implants)
- Additional psychiatric or neurological conditions / Additional major comorbidities
- History of severe head injury
- Participation in another trial
- Pregnancy and breastfeeding
- Inability to understand information about the protocol
- Persons deprived of their liberty by judicial or administrative decision
- Adult subject under legal protection or unable to consent.
- Unwillingness to be informed in case of abnormal MRI
- Treatment with tetrabenazine
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Validation of Molecular Neuroimaging Biomarkers in Huntington's Disease in View of Therapeutic Trials Targeting the Krebs Cycle
There is no curative treatment available today in Huntington disease (HD) despite the identification of the mutated gene 20 years ago. Nonetheless, safe and promising therapeutic strategies targeting brain energy metabolism are now becoming available.
In view of the small effect sizes of any clinical parameter in HD, robust neuroimaging biomarkers reflecting brain energy metabolism are therefore urgently needed to better assess the potential of therapeutics targeting the mitochondria, and especially the Krebs cycle. Identifying such biomarkers at the presymptomatic phase in HD also provides a unique window for therapeutic intervention, which can be used as a proof-of-concept for the real challenge of tomorrow's medicine: the prevention of neurodegeneration HDeNERGY is an observational study consisting of the transfer of methods from preclinical to clinical studies and their application in HD. HDeNERGY aim at optimizing MRI/MRS methods to study the dynamics of brain energy metabolism. At the CENIR (Centre de neuro-imagerie et de recherche, Paris) the determination of creatine kinase rate will be first validated in healthy volunteers (n=20) and then applied to the selected cohort of early affected HD patients (n=20), presymptomatic individuals (n=20) and controls (n=20) together with the methods previously validated in HD patients (Mochel et al., 2012b) to determine the ratio of inorganic phosphate (Pi)/ phosphocreatine (PCr) during visual stimulation in presymptomatic individuals. The Chemical Exchange Saturation Transfer (CEST) method on the 3T clinical scanner of CENIR will be first validated in healthy volunteers (n=20) and then applied to the selected cohort of early affected HD patients (n=20), presymptomatic individuals (n=20) and controls (n=20).
The cerebral synthesis rate of creatine phosphate and of brain glutamate concentrations and pH values will be compared between controls, HD patients and HD presymptomatic individuals, and correlated with clinical parameters (age, BMI, UHDRS).
Read the detailed description
Compelling evidence indicate a key role of energy defects in neurodegenerative diseases (NDs). These defects would constitute extremely informative functional biomarkers of disease states and progression. Such functional biomarkers could be used as readouts for therapeutic efficacy in clinical trials, especially for drugs targeting brain energy metabolism. Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) are likely the most promising approaches to validate brain biomarkers linked to energy metabolism. However, existing methods allowing "static" measures of metabolites concentrations offer only a fragmented vision of brain energy metabolism in NDs. The validation of novel and "dynamic" methods is urgently needed. Our project addresses this challenge for Huntington disease (HD).
Our study is an observational study consisting of the transfer of methods from preclinical to clinical studies and their application in HD.
This study comprises two period:
- Period 1: transfer of 31P saturation transfer and CEST methods from preclinical to clinical MRS/MRI platforms and the validation of these methods in healthy individuals;
- Period 2: compare brain metabolic markers in early individuals affected by HD, presymptomatic individuals and controls, using 31P saturation transfer and CEST methods.
The primary objectives are:
Using 31P saturation transfer and CEST methods, the primary objective is to compare novel metabolic biomarkers between controls and HD carriers (patients and presymptomatic individuals).
Assessment criterion:
Comparison between controls, HD patients and HD presymptomatic individuals of the cerebral synthesis rate of creatine phosphate and of brain glutamate concentrations and pH values
The secondary objectives are:
- To develop/optimize 31P MRS/CEST methods to study the dynamics of brain energy metabolism in humans
- To improve the understanding and "modeling" the nature of energy deficits in HD
- To look for correlations between brain energy profiles and clinical scores.
Assessment criteria:
- Validation of the 31P MRS and CEST methods in healthy volunteers.
- Combination and integration of the 31P MRS and CEST data in order to obtain a model of energy deficits in HD.
- Correlations between creatine phosphate synthetic rate and clinical parameters (age, BMI, UHDRS); correlations between glutamate concentrations and clinical parameters; correlations between pH values and clinical parameters.
Ancillary studies:
The investigators wish to compare brain energy parameters (creatine phosphate synthetic rate, glutamate concentrations, pH values) with systemic metabolic markers (profiles of plasma metabolites obtained from metabolomic and lipidomic studies).
- Keywords
- Huntington disease, Neuroimaging metabolic biomarker
- Medical subject headings
- Huntington Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| healthy volunteers | 31P-MR Spectroscopy and CEST for Validation of MRI/MRS methods | |
| HD presymptomatic individuals | General medical exam Clinical assessment with illness rating scales: Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS) and Total Functional Capacity (TFC), 31P-MR Spectroscopy and CEST | |
| early affected HD patients | General medical exam Clinical assessment with illness rating scales: UHDRS and TFC, 31P-MR Spectroscopy and CEST | |
| Controls | General medical exam Clinical assessment with illness rating scales: UHDRS and TFC, 31P-MR Spectroscopy and CEST |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral synthesis rate of creatine phosphate
Comparison between controls, HD patients and HD presymptomatic individuals of the cerebral synthesis rate of creatine phosphate
Measured: 1 day
Cerebral brain glutamate concentrations
Comparison between controls, HD patients and HD presymptomatic individuals of brain glutamate concentrations
Measured: 1 day
Cerebral pH values.
Comparison between controls, HD patients and HD presymptomatic individuals of pH values
Measured: 1 day
Secondary outcomes (11)
Measure concentration of brain phosphocreatine (PCr) and glutamate using 31P MRS and gluCEST respectively in healthy volunteers
The 31P MRS will allow to measure the synthesis rate of PCr at different time points - rest, visual stimulation and recovery after stimulation. The rate of PCr synthesis will give an indication on the integrity of the rate of creatine-kinase.
gluCEST will allow to measure the regional distribution of glutamate in the brain in order to create glutamate maps.
Measured: 1 day
Data integration of rate of phosphocreatine (PCr) synthesis and gluatamate concentrations.
A model of energy deficit in HD can be created by looking at the correlation between the rate of PCr synthesis, glutamate maps and the disease.
Measured: 1 day
Correlations between the ratio of phosphocreatine concentration at different time point and age of participants
Measured: 1 day
Correlations between the ratio of phosphocreatine concentration at different time points and BMI of participants.
Measured: 1 day
Correlations between creatine phosphate synthetic rate and UHDRS
Measured: 1 day
Correlations between glutamate concentrations and age
Measured: inclusion visit
Correlations between glutamate concentrations and BMI
Measured: inclusion visit
Correlations between glutamate concentrations and UHDRS
Measured: 1 day
Correlations between pH values and age
Measured: 1 day
Correlations between pH values and BMI
Measured: 1 day
Correlations between pH values and UHDRS
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2015 (estimated)
- Study start28 Jun 2016
- Primary completion24 Jun 2019
- Study completion24 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Neuroimaging Biomarkers in Huntington DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- CEA
- Responsible party
- Sponsor
- Investigators
- Fanny MOCHEL, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02639871
- Sponsor's protocol ID
- P140708
- Other IDs
- 2015-A00793-46
- Acronym
- HDeNERGY
- Status last verified
- Aug 2019
- First submitted
- 15 Dec 2015
- Last updated
- 8 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of Molecular Neuroimaging Biomarkers in Huntington's Disease in View of Therapeutic Trials Targeting the Krebs Cycle
- ClinicalTrials.gov ID
- NCT02639871
- Acronym / sponsor ID
- HDeNERGY / P140708
- Keywords
- Huntington disease, Neuroimaging metabolic biomarker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- CEA
- Study start
- 28 Jun 2016 (actual)
- Primary completion
- 24 Jun 2019 (actual)
- Study completion
- 24 Jun 2019 (actual)
- First posted
- 28 Dec 2015 (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.
There is no curative treatment available today in Huntington disease (HD) despite the identification of the mutated gene 20 years ago. Nonetheless, safe and promising therapeutic strategies targeting brain energy metabolism are now becoming available.
In view of the small effect sizes of any clinical parameter in HD, robust neuroimaging biomarkers reflecting brain energy metabolism are therefore urgently needed to better assess the potential of therapeutics targeting the mitochondria, and especially the Krebs cycle. Identifying such biomarkers at the presymptomatic phase in HD also provides a unique window for therapeutic intervention, which can be used as a proof-of-concept for the real challenge of tomorrow's medicine: the prevention of neurodegeneration HDeNERGY is an observational study consisting of the transfer of methods from preclinical to clinical studies and their application in HD. HDeNERGY aim at optimizing MRI/MRS methods to study the dynamics of brain energy metabolism. At the CENIR (Centre de neuro-imagerie et de recherche, Paris) the determination of creatine kinase rate will be first validated in healthy volunteers (n=20) and then applied to the selected cohort of early affected HD patients (n=20), presymptomatic individuals (n=20) and controls (n=20) together with the methods previously validated in HD patients (Mochel et al., 2012b) to determine the ratio of inorganic phosphate (Pi)/ phosphocreatine (PCr) during visual stimulation in presymptomatic individuals. The Chemical Exchange Saturation Transfer (CEST) method on the 3T clinical scanner of CENIR will be first validated in healthy volunteers (n=20) and then applied to the selected cohort of early affected HD patients (n=20), presymptomatic individuals (n=20) and controls (n=20).
The cerebral synthesis rate of creatine phosphate and of brain glutamate concentrations and pH values will be compared between controls, HD patients and HD presymptomatic individuals, and correlated with clinical parameters (age, BMI, UHDRS).
Detailed description
Compelling evidence indicate a key role of energy defects in neurodegenerative diseases (NDs). These defects would constitute extremely informative functional biomarkers of disease states and progression. Such functional biomarkers could be used as readouts for therapeutic efficacy in clinical trials, especially for drugs targeting brain energy metabolism. Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) are likely the most promising approaches to validate brain biomarkers linked to energy metabolism. However, existing methods allowing "static" measures of metabolites concentrations offer only a fragmented vision of brain energy metabolism in NDs. The validation of novel and "dynamic" methods is urgently needed. Our project addresses this challenge for Huntington disease (HD).
Our study is an observational study consisting of the transfer of methods from preclinical to clinical studies and their application in HD.
This study comprises two period:
- Period 1: transfer of 31P saturation transfer and CEST methods from preclinical to clinical MRS/MRI platforms and the validation of these methods in healthy individuals;
- Period 2: compare brain metabolic markers in early individuals affected by HD, presymptomatic individuals and controls, using 31P saturation transfer and CEST methods.
The primary objectives are:
Using 31P saturation transfer and CEST methods, the primary objective is to compare novel metabolic biomarkers between controls and HD carriers (patients and presymptomatic individuals).
Assessment criterion:
Comparison between controls, HD patients and HD presymptomatic individuals of the cerebral synthesis rate of creatine phosphate and of brain glutamate concentrations and pH values
The secondary objectives are:
- To develop/optimize 31P MRS/CEST methods to study the dynamics of brain energy metabolism in humans
- To improve the understanding and "modeling" the nature of energy deficits in HD
- To look for correlations between brain energy profiles and clinical scores.
Assessment criteria:
- Validation of the 31P MRS and CEST methods in healthy volunteers.
- Combination and integration of the 31P MRS and CEST data in order to obtain a model of energy deficits in HD.
- Correlations between creatine phosphate synthetic rate and clinical parameters (age, BMI, UHDRS); correlations between glutamate concentrations and clinical parameters; correlations between pH values and clinical parameters.
Ancillary studies:
The investigators wish to compare brain energy parameters (creatine phosphate synthetic rate, glutamate concentrations, pH values) with systemic metabolic markers (profiles of plasma metabolites obtained from metabolomic and lipidomic studies).
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| healthy volunteers | – | –31P-MR Spectroscopy and CEST for Validation of MRI/MRS methods |
| HD presymptomatic individuals | – | –General medical exam Clinical assessment with illness rating scales: Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS) and Total Functional Capacity (TFC), 31P-MR Spectroscopy and CEST |
| early affected HD patients | – | –General medical exam Clinical assessment with illness rating scales: UHDRS and TFC, 31P-MR Spectroscopy and CEST |
| Controls | – | –General medical exam Clinical assessment with illness rating scales: UHDRS and TFC, 31P-MR Spectroscopy and CEST |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Period 1: healthy volunteers; Period 2: presymptomatic individuals, early affected HD patients and controls
Key inclusion criteria (32 listed)
- At least 18 years of age
- Signature of the informed consent
- Covered by social security
- At least 18 years of age
- Signature of the informed consent
Key exclusion criteria (0 listed)
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
Cerebral synthesis rate of creatine phosphate
Time frame: 1 day
Comparison between controls, HD patients and HD presymptomatic individuals of the cerebral synthesis rate of creatine phosphate
Cerebral brain glutamate concentrations
Time frame: 1 day
Comparison between controls, HD patients and HD presymptomatic individuals of brain glutamate concentrations
Cerebral pH values.
Time frame: 1 day
Comparison between controls, HD patients and HD presymptomatic individuals of pH values
11 secondary outcomes
Measure concentration of brain phosphocreatine (PCr) and glutamate using 31P MRS and gluCEST respectively in healthy volunteers
Time frame: 1 day
Data integration of rate of phosphocreatine (PCr) synthesis and gluatamate concentrations.
Time frame: 1 day
Correlations between the ratio of phosphocreatine concentration at different time point and age of participants
Time frame: 1 day
Correlations between the ratio of phosphocreatine concentration at different time points and BMI of participants.
Time frame: 1 day
Correlations between creatine phosphate synthetic rate and UHDRS
Time frame: 1 day
Correlations between glutamate concentrations and age
Time frame: inclusion visit
Correlations between glutamate concentrations and BMI
Time frame: inclusion visit
Correlations between glutamate concentrations and UHDRS
Time frame: 1 day
Correlations between pH values and age
Time frame: 1 day
Correlations between pH values and BMI
Time frame: 1 day
Correlations between pH values and UHDRS
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2019.
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.
Fanny MOCHEL, MD principal investigator
Assistance Publique - Hôpitaux de Paris
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 Brain Neuroimaging Biomarkers in Huntington Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 32 inclusion and 0 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: finished, as of the sponsor's last update on 8 Aug 2019. 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 France. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cerebral synthesis rate of creatine phosphate (time frame: 1 day). The study lists 3 primary outcomes in all. 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 8 Aug 2019.