Exploration of Differences in Metabolite Concentrations by 7Teslas NMR Spectroscopy in Striatum and Subthalamic Nuclei in de Novo Parkinsonian Patients and Control Subjects

NCT04735172 | Recruiting

• 2 other identifiers: AOI 2020 DURIF (METABO-NGC-7T)2020-A03237-32
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

Initially, the exploration of brain metabolism by Nuclear Magnetic Resonance Spectroscopy (MRS) of the high magnetic field proton (1H) (11.7T) applied to acute and chronic animal models of Parkinson's disease (PD) showed glutamatergic hyperactivity within the striatum, one of the components of the basal ganglia. Interestingly, acute administration of L-dopa and acute, subchronic and chronic deep brain stimulation of the subthalamic nucleus (STN) normalizes these neurochemical profiles. Investigators also show an increase in glutamate levels in the STN ipsilateral to the substantia nigra pars compacta (SNpc) damaged by the neurotoxin, expected phenomenon, but also and surprisingly in the STN controlateral to the lesion. A degeneration of dopaminergic neurons is also observed in the controlateral SNpc at the lesion suggesting that the hyperglutamatergy of the controlateral STN to the lesion could promote neuronal death in the SNpc and thus participate in the progression and lateralization of the PD. Using 3T MRS in PD patients, as in other studies in humans, investigators do not see changes in glutamate and glutamine levels in the putamen of Parkinsonian patients. This difference between animal and human studies can be explained:

1. 1.by the different rate of progression between PD in humans and animal models with plasticity phenomena limiting glutamatergic hyperactivity,
2. 2.by the effect of treatment in PD masking changes in glutamate metabolism,
3. 3.by limiting sensitivity in the detection of metabolites (Glutamate, glutamine, GABA) at 3T.

Conditions

Parkinson's Disease

Keywords

De novo Parkinson's disease,; 1H Magnetic Resonance Spectroscopy,; 7 Teslas,; putamen,; Subthalamic nucleus,; glutamate,; glutamine

Outcome Measures

Primary Outcomes (1)

• Glutamate concentration (mmol.L-1) measured in the putamen

  The concentration of glutamate present on the 1H NMR spectra obtained in vivo will be quantified using Lcmodel software (Provencher 1993). It is a quantification algorithm for modelling the background noise inherent in NMR signals. This quantification method uses a database of NMR signals from the various brain metabolites simulated by quantum mechanics through their chemical and constant coupling movements (Govindaraju \& al., 2000; Tkáč \& al., 2005). The following 8 metabolites are included in the database: Creatine, Choline, Glutamate, Glutamine, Lactate, Myo-Inositol, N-acetylaspartate and Taurine.

  day 90

Secondary Outcomes (10)

• Glutamate concentration (mmol.L-1) measured in STN (right and left).

  day 90

• NMR spectroscopy measurements of choline,in the central grey nuclei, striatum (right and left), and NST (right and left)(mmol.L-1).

  day 90

• NMR spectroscopy measurements of myoinositol in the central grey nuclei, striatum (right and left), and NST (right and left)(mmol.L-1).

  day 90

• NMR spectroscopy measurements of N-acetylaspartate in the central grey nuclei, striatum (right and left), and NST (right and left)(mmol.L-1).

  day 90

• NMR spectroscopy measurements of creatine in the central grey nuclei, striatum (right and left), and NST (right and left)(mmol.L-1).

  day 90

Study Arms (2)

de novo PD patients

EXPERIMENTAL

Patients will be included: * suffering from idiopathic Parkinson's disease according to UKPDSBB criteria (Gibb \& Lees, 1988; Hughes et al., 1992), * the stage of the disease is I-II according to the Hoehn and Yahr scale, * which do not receive dopaminergic treatment, * duration of disease development: 5 years, * without major cognitive impairment (Moca \> 24) * men or women aged 18 to 75, * having understood and signed the informed consent form, * members of a social security scheme.

Other: specific MRI Acquisition (NMR spectroscopy) at 7T

control subjects

EXPERIMENTAL

* subjects male or female aged 18 -75 years * subjects affiliated to a social security scheme. * volunteers who have given their written consent. They will be matched to de novo PD patients according to age, sex and level of education.

Other: specific MRI Acquisition (NMR spectroscopy) at 7T

Interventions

specific MRI Acquisition (NMR spectroscopy) at 7T OTHER

The MRI protocol will be performed at 7T on a Siemens NMR imaging system (Magnetom Terra, Siemens Healthcare, Erlangen, Germany), the radio frequency emission and signal reception will be done through a head quadrature resonator (64-channel phase-array coil). To avoid motion-related artifacts, the patient will be seated in a supine position, with the arms along the body and the head immobilized using a suitable head restraint. The MR protocol will take place in two phases: * Acquisition of 3D multi-slice T1 and T2-weighted morphological images to identify areas of interest; * Acquisition of 1D RMN spectra in the right and left putamen and STN. Spectra will be acquired in volumes of interest of 15mmx15mmx15mm using a localized spectroscopy sequence with and without suppression of the water signal. Main parameters are: TR (repetition time)=3000ms; TE (echo time)=20 ms; number of repetitions=128; scan time 6min).

control subjects; de novo PD patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be included:
• suffering from idiopathic Parkinson's disease according to UKPDSBB criteria (Gibb \& Lees, 1988; Hughes et al., 1992),
• the stage of the disease is I-II according to the Hoehn and Yahr scale,
• which do not receive dopaminergic treatment,
• duration of disease development 5 years,
• without major cognitive impairment (Moca \> 24)
• men or women aged 18 to 75,
• having understood and signed the informed consent form,
• members of a social security scheme.
• Controls:
• subjects male or female aged 18 -75 years
• subjects affiliated to a social security scheme.
• volunteers who have given their written consent.

You may not qualify if:

• Patients will be excluded:
• having a severe tremor (\> 3 for a trembling sub-item of UPDRS 3) making the MR examination impossible,
• patients with "contra-indications" to an MRI exam (without administration of a gadolinium chelate): presence of metal parts in the body (electronic devices such as a pacemaker, a neurostimulator, a cochlear implant, prostheses, etc.), claustrophobia,
• taking any treatment that may interact with brain concentrations of neurotransmitters, such as all psychotropic drugs and in particular antidepressants, neuroleptics, benzodiazepines, antiepileptics,
• pregnant women,
• treated by deep brain neurostimulation,
• patients under guardianship or guardianship or protection of justice,
• patients who are excluded from another study.
• Controls:
• persons suffering from progressive neurological and psychiatric pathology,
• persons with "contra-indications" to an MRI examination (without administration of a gadolinium chelate): presence of metal parts in the body (electronic devices such as a pacemaker, a neurostimulator, a cochlear implant, prostheses, etc.), claustrophobia,
• taking any treatment that may interact with brain concentrations of neurotransmitters, such as: all psychotropic drugs and in particular antidepressants, neuroleptics, benzodiazepines, antiepileptics,
• pregnant women,
• persons under guardianship or trusteeship or protection of justice,
• people who are excluded from another study.

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (2)

Chu Clermont Ferrand

Clermont-Ferrand, 63003, France

NOT YET RECRUITING

CHU Poitiers

Poitiers, France

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Ana Rachel MARQUES

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lise Laclautre

CONTACT

334.73.754.963; promo_interne_drci@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2021
• First Posted: February 3, 2021
• Study Start: April 7, 2022
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

FR (2)