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Trial record 53 of 158 for:    genetics AND Parkinson's disease

Compensation Mechanisms in Parkinson's Disease (DATACOMT)

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ClinicalTrials.gov Identifier: NCT02869945
Recruitment Status : Recruiting
First Posted : August 17, 2016
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Parkinson's disease onset is clinically defined as the appearance of motor symptoms including akinesia, tremor and hypertonia. Several studies have shown that motor symptoms occur when at least 50 % of dopaminergic neurons are lost. However, there are evidence suggesting that the level of dopaminergic denervation is not homogenous at the time of diagnosis.

Some patients have a higher level of dopaminergic loss at disease onset indicating the existence of compensation mechanisms. The aim of this study is to decipher how the metabolism of dopamine is involved in this compensation with a focus on the polymorphism of the COMT gene. This gene is expressed according to two variant: (i) COMT H that encodes a form of the enzyme with a high level of activity and (ii) COMT L that encode a form of the enzyme with a low level of activity. Thus, there are 3 possible genotypes in the population: (i) COMT HH associated with an increased degradation of dopamine, (ii) COMT LL associated with a decreased degradation of dopamine and (iii) COMT HH (intermediary between COMT HH and COMT LL).

The hypothesis is that this polymorphism of the COMT gene may participate to compensation mechanisms in early PD. Patients with COMT HH genotype may have an earlier motor symptoms onset than patients with COMT LL genotype.

To test this hypothesis, we will recruit 51 patients with de novo PD will be recruited (17 patients for each genotype). Given the distribution of COMT polymorphism in the population, a maximum sample of 76 patients will be screened to recruit 17 patients for each genotype.

Clinical evaluation will include MDS-UPDRS, Non Motor Symptoms Scale, segmental symptoms scale, Montreal Cognitive assessment, MMSE, Frontal assessment battery and Parkinson's disease behavioral assessment scale (ECMP). All the patients will have a monophotonic emission tomography with I-123-Ioflupane in order to assess the level of dopaminergic denervation and an MRI scan with resting state study. Cerebrospinal fluid sampling will be optional and will allow direct measurements of dopamine metabolites.

The main outcome measure will be the level of dopaminergic denervation on I-123-Ioflupane scans according to COMT genotype, age, gender and severity of motor symptoms on the MDS-UPDRS part 3.

If this hypothesis is confirmed, this will allow to test the efficacy of COMT inhibitors in order to delay dopaminergic drugs initiation for PD patients.


Condition or disease Intervention/treatment Phase
Parkinson Disease Genetic: Identification of COMT HH, COMT HL or COMT LL genes Other: Brain MRI with resting state scan Other: Brain MPET Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 51 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Dopaminergic Denervation and COMT Polymorphism in de Novo Patients With Parkinson's Disease
Actual Study Start Date : September 2016
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
COMT HH
COMT HH gene
Genetic: Identification of COMT HH, COMT HL or COMT LL genes
COMT HH, COMT HL or COMT LL genes identification

Other: Brain MRI with resting state scan
MRI scan with resting state study to be performed to assess the compensation mechanisms at the networks level.

Other: Brain MPET
Monophotonic emission tomography with I-123-Ioflupane to assess the level of dopaminergic denervation.

COMT HL
COMT HL gene
Genetic: Identification of COMT HH, COMT HL or COMT LL genes
COMT HH, COMT HL or COMT LL genes identification

Other: Brain MRI with resting state scan
MRI scan with resting state study to be performed to assess the compensation mechanisms at the networks level.

Other: Brain MPET
Monophotonic emission tomography with I-123-Ioflupane to assess the level of dopaminergic denervation.

COMT LL
COMT LL gene
Genetic: Identification of COMT HH, COMT HL or COMT LL genes
COMT HH, COMT HL or COMT LL genes identification

Other: Brain MRI with resting state scan
MRI scan with resting state study to be performed to assess the compensation mechanisms at the networks level.

Other: Brain MPET
Monophotonic emission tomography with I-123-Ioflupane to assess the level of dopaminergic denervation.




Primary Outcome Measures :
  1. Comparison of the degree of presynaptic dopaminergic denervation across the 3 genotypes group (COMT HH, COMT HL and COMT LL) at the time of diagnostic of Parkinson disease [ Time Frame: Within 3 months after inclusion ]
    The degree of presynaptic dopaminergic denervation estimated by the potential links of 123I-FP-CIT (radioligand dopamine transporter) on scintigraphy images of single photon emission


Secondary Outcome Measures :
  1. Degree of presynaptic denervation in three groups: COMT HH, COMT LL, COMT HL with and without adjustment for age, sex and UPDRS III score [ Time Frame: Within 3 months after inclusion ]
  2. CSF dopamine metabolite levels at the time of diagnosis (CSF sampling will be optional) in the groups COMT HH, COMT HL and COMT LL [ Time Frame: Within 3 months after inclusion ]
  3. Functional connectivity resting MRI Index obtained by full integration and graph theory based on genotypes (COMT HH, COMT LL, COMT HL) and denervation degree (MPET). [ Time Frame: Within 3 months after inclusion ]
  4. MDS UPDRS-III motor score according to the genotypes (COMT HH, COMT LL, COMT HL) and denervation degree observed by MPET [ Time Frame: Within 3 months after inclusion ]


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

Inclusion Criteria:

  • Man or woman ≥ 18 years old,
  • Caucasian origin
  • Parkinson's disease considered to be probable as defined by the criteria of UK Parkinson's disease Brain Bank (Hugues and coll 2002)
  • Absence of anti-parkinsonian medication
  • Patient affilied to a social security system
  • Signed information consent form

Exclusion Criteria:

  • Parkinsonian syndrome secondary to neuroleptics
  • Atypical parkinsonian syndrome such a multisystem atrophy, progressive supranuclear paralysis, dementia with levy bodies.
  • MRI contraindication (claustrophobia, not compatible mechanical heart valve MRI, pacemaker, cochlear implant, other body ferromagnetic objects, pregnancy) - MPET contraindication (pregnancy, feeding, hypersensitivity to ioflupane [123]
  • Realization of a nuclear medicine examination in the year before the patient's inclusion - Patient under guardianship or trusteeship
  • Any other significant pathology that could prevent patient participation and achievement of planned examinations (except for lumbar puncture)
  • Patient participating or having participated in other biomedical research involving a drug in the three months prior to inclusion
  • Specific exclusion criteria if lumbar puncture is accepted by the patient: Anticoagulation or antiplatelet treatment; history of hemostasis disorders; platelets <150,000 mm3; TP <80%; TCA (patient / control)> 1.2.
  • Hypersensitivity to local anesthetics with amide link or to any of the excipients

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 ClinicalTrials.gov identifier (NCT number): NCT02869945


Contacts
Contact: David Grabli, MD-PhD 0033 1 42 16 24 61 david.grabli@aphp.fr
Contact: Jean- Christophe Corvol, PUPH 0033 1 42 16 57 66 jean-chistophe.corvol@aphp.fr

Locations
France
Groupe Hospitalier Pitié-Salpêtrière Recruiting
Paris, France, 75013
Contact: David GRABLI, Dr         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: David Grabli, MD-PhD Assistance Publique - Hôpitaux de Paris

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02869945     History of Changes
Other Study ID Numbers: P130939
First Posted: August 17, 2016    Key Record Dates
Last Update Posted: April 17, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
de novo untreated Parkinson Disease
genetic
COMT Polymorphism
gene
brain MRI
brain MPET

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases