Assessment of the impairment of the serotoninergic system during the prodromal phase of Parkinson’s disease in SNCA mutation carriers by PET using [11C]DASB and [11C]SB207145 : SerIAL-PD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut National De La Sante Et De La Recherche Medicale

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Pathological Conditions, Signs and Symptoms [C23], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Decision date (initial)

2025-08-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Agence nationale de la recherche (ANR)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis

To investigate the early alteration of the serotoninergic system at the prodromal stage of Parkinson’s disease (PD) using the radiotracers [11C]DASB and [11C]SB207145 in participants with alpha-synuclein SNCA gene mutations (SNCA+ PD-), compared with healthy controls (SNCA- PD-).

Secondary objectives 5

1. To investigate the evolution of the serotoninergic system in the continuum of PD progression from the prodromal stage to the symptomatic stage
2. To investigate the correlation between serotoninergic alterations, and motor and non-motor symptoms, in the continuum of PD course
3. To investigate the correlation between serotoninergic alterations and dopaminergic alterations in the continuum of PD course
4. To investigate the correlation between serotoninergic alterations, dopaminergic alterations, motor and non-motor symptoms, and wet biomarkers in the continuum of PD course
5. To investigate anatomical and functional changes on MRI between groups and measure specific correlations with clinical scores

Conditions and MedDRA coding

Parkinson's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Males and females with an age range of 18–80 years at the time of signing the informed consent
2. Diagnosis of PD according to the 2015 Movement Disorder Society criteria, with bradykinesia AND at least ONE of the following: muscular rigidity, or resting tremor; with no other suspected cause of Parkinsonism for Symptomatic PD patients with and without SNCA mutation
3. With documented point mutation or multiplication (i.e., duplication/triplication) mutation on the α-synuclein gene (SNCA) for Symptomatic PD patients with and without SNCA mutation
4. Or without documented mutation in the SNCA gene for Symptomatic PD patients with and without SNCA mutation
5. First degree relative of a PD patient with a known point mutation or multiplication in the SNCA gene (parent, sibling, or child) for Relatives of SNCA gene mutation carriers, without a diagnosis of PD
6. Asymptomatic for PD symptoms, and not meeting Diagnosis of PD according to the 2015 Movement Disorder Society criteria for Healthy controls and Relatives of SNCA gene mutation carriers, without a diagnosis of PD
7. Able to perform the assessments planned for the study (including brain imaging) according to investigator opinion
8. Informed consent obtained from the patient or/ and a legal representative when appropriate
9. For subjects taking any of the following drugs (Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative) must be willing and medically able to hold the medication for at least 5 half-lives before DaTSCAN imaging.
10. Participant affiliated with or beneficiary of a French social security system or of such a regime

Exclusion criteria 17

1. Contraindication to MRI such as claustrophobia, epilepsy, severe movement disorders or inability to lay flat that, in the investigator's judgment, precludes the subject's safe participation in and completion of the study. Subjects with a history of working with metal (using grinders, etc.) should have a safety check for residual metal fragments in their eyes to avoid damage from the magnetic fields.
2. Implanted devices such as stimulators, spinal rods, aneurysm clips, cardiac pacemaker, hearing device, metallic contraceptive device, insulin pump, artificial implants, peripheral or neuronal stimulator, intravenous catheter that would interfere with MRI interpretation
3. Contraindication to PET imaging or DaTSCAN®
4. Known Hypersensitivity to ioflupane or to any excipients of DaTSCAN®
5. Significant brain abnormalities that could interfere with accurate brain imaging analysis
6. Subjects treated with specific serotonin reuptake inhibitors, noradrenalin or serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase type A inhibitors, neuroleptics impacting the serotoninergic system or recreative drugs impacting the serotonergic system in the last 3 months
7. Impaired comprehension interfering with an informed consent in the opinion of the investigator
8. Pregnant and lactating women; Women of childbearing potential (WOCBP) tested positive in serum or urine pregnancy test (The following may be considered as highly effective contraception: progestogen-only or combined (estrogen and progestogen containing) hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner (if the 22/58 SerIAL-PD_Protocol_V1.0_18032025 partner is the sole sexual partner of the WOCBP participant for the duration of the study) or abstinence (depending on the participant's lifestyle)).
9. WOCBP without a highly effective contraception
10. Participation in investigational drug trials within 30 days prior to screening or within 5 half-life of investigational product whatever the longest
11. Active disease which could interfere with study conduct as per investigator’s judgement
12. Any factor which might create an unjustified risk for the participant
13. Minors or subjects benefiting from laws aimed at protecting vulnerable adults: subjects being deprived of liberty by judicial or administrative decision, subjects under guardianship /curatorship.
14. For participants undergoing optional lumbar puncture (LP): Any contraindication to LP procedures, including but not limited to: a. Known or suspected structural abnormality of the lumbar spine, including but not limited to X-ray, MRI, or myelographic evidence of significant lumbar spine abnormalities, or other anatomical factors at or near the LP site that, in the opinion of the Investigator, may interfere with the performance of the LP, render repeated LPs difficult, or increase the risk of the procedure for the participant. b. Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and might place a participant at an increased risk for intraoperative or postoperative bleeding. These could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities), known underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, von Willebrand’s disease, liver disease), clinically significant abnormal lab values increasing the risk of bleeding regarding platelets count, INR or PT or aPTT. - Low platelet count (below 50,000 cells/μL)(Hemostasis test must be done 72h max prior to the LP. A medical prescription will be sent to the participant to check whether his/her coagulation level is in accordance with this intervention.), - Screening values of International Normalized Ratio (INR), Prothrombin time (PT), or Activated Partial Thromboplastin Time (APTT) that are not within normal ranges (determined by the laboratory performing the analyses), - Taking any antiplatelet medication (e.g., aspirin >81 mg daily, clopidogrel, or nonsteroidal anti-inflammatory drugs [NSAIDs]) within 7 days prior to the planned LP or anticipated need for antiplatelet medication within 48 hours after an LP, - Taking anticoagulant medication (warfarin, heparinoids, and direct coagulation factor inhibitors, e.g., apixaban, dabigatran, rivaroxaban) c. Presence of intracranial hypertension d. Puncture site infections e. Patients treated with Deep Brain Stimulation.
15. For participants undergoing optional skin sampling: any contraindication to this procedure including : - Anticoagulant or antiplatelet therapy, - History of hemostasis disorders, - Bleeding risk verified by a coagulation test
16. Presence or known medical history of clinically significant neurological disorder other than PD
17. Participant within the exclusion period in the National Register for participants of the French Ministry of Health.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Determine PET-binding potential of radiotracer ligands [11C]DASB and [11C]SB207145 to respective serotonin transporter SERT and receptor 5-HT4, and compare between SNCA+ PD- participants and SNCA- PD- participants.

Secondary endpoints 5

1. Determine PET-binding potential of radiotracer ligands [11C]DASB and [11C] SB207145, and compare results between all groups.
2. Determine correlations between PET-binding potential of radiotracer ligands [11C]DASB and [11C] SB207145 and scores on motor and non-motor symptom assessment scales, and compare results between all groups.
3. Determine correlations between PET-binding potential of radiotracer ligands [11C]DASB and [11C] SB207145, DaTSCAN results, and neuromelanin-sensitive MRI (NM-MRI)) results, and compare results between all groups.
4. Determine correlations between PET-binding potential of radiotracer ligands [11C]DASB and [11C] SB207145, DaTSCAN results, neuromelanin-sensitive MRI (NM-MRI) results, scores on motor and non-motor symptom assessment scales, and measurements of blood and cerebrospinal biomarkers, and compare results between all groups.
5. Determine the difference between anatomical and functional MRI images between groups and correlations with clinical scores and PET data.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut National De La Sante Et De La Recherche Medicale

Sponsor organisation

Institut National De La Sante Et De La Recherche Medicale

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Institut National De La Sante Et De La Recherche Medicale

Contact name

SGAMBATO Véronique

Public contact point

Organisation

Institut National De La Sante Et De La Recherche Medicale

Contact name

Principal Investigator: CORVOL Jean-Christophe

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications