SUL-238 effects on brain energy (31P‑MRS) in early, untreated Parkinson's disease

A Phase 2, Randomized, Double-blind, Placebo-Controlled, Single-Center Study to Assess the Effects of SUL-238 on High Energy Phosphates With Magnetic Resonance Spectroscopy (³¹P-MRS) in Patients With Early, Untreated Parkinson's Disease ("SHEPHERD" STUDY)

This study will test whether taking SUL-238 for 28 days improves brain mitochondrial energy markers in people with early, untreated Parkinson's disease, using 31P‑MRS scans and a placebo comparison.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 40 Years and up
• Sex: All
• Sponsor: GEN İlaç ve Sağlık Ürünleri A.Ş. (Industry-sponsored)
• Locations: 1 site (Groningen)
• Trial ID: NCT07322887 on ClinicalTrials.gov

What this trial studies

This randomized, double‑blind Phase 2 study enrolls people with early, untreated Parkinson's disease and randomizes them 1:1:1 to high‑dose SUL‑238, low‑dose SUL‑238, or placebo for 28 days. The primary outcome is change in high‑energy phosphate measures in the brain assessed by 31P‑MRS; safety and tolerability are also monitored. Participants visit the clinic for dosing and blood draws on days 1, 14, 28, and 56, and a subset may provide CSF on day 28. The study is small (about 15 patients per arm) and is conducted at a single site in the Netherlands.

Who should consider this trial

Good fit: Adults aged 40 or older with Parkinson's disease diagnosed within the past year who are treatment‑naive, have Hoehn and Yahr stage ≤1 and MoCA ≥22, and can attend required clinic visits and MRI/MRS scans.

Not a fit: People with more advanced Parkinson's, those already taking antiparkinsonian medications, significant cognitive impairment, MRI contraindications, or who cannot travel to the study site are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If SUL‑238 improves mitochondrial energy markers, it could point to a new approach to protect or slow early Parkinson's disease progression.

How similar studies have performed: Mitochondrial‑targeting treatments have supportive preclinical data and limited early human work, and 31P‑MRS is an established biomarker method, but clear clinical benefit in Parkinson's disease has not yet been demonstrated.

Eligibility criteria

Inclusion Criteria:

1. Untreated Parkinson's Disease (PD) patients diagnosed in accordance with the UK PDS Brain Bank Criteria for the diagnosis of PD. Patients must have bradykinesia and at least one of the following:

   1. muscular rigidity
   2. rest tremor (4-6 Hz)
   3. postural instability unrelated to primary visual, cerebellar, vestibular or proprioceptive dysfunction.
2. The duration of PD since diagnosis is ≤ 1 year.
3. Patients with Modified Hoehn and Yahr stage ≤ 1.0.
4. Patients with Montreal Cognitive Assessment (MOCA) score of ≥22.
5. Men and women aged ≥40 years at screening.
6. Able to understand the nature of the study and provide signed and dated written informed consent in accordance with local regulations before the conduct of any study related procedures.
7. Able to complete all study related testing and evaluations.
8. Patients must be, in the opinion of the Investigator, able to participate in all scheduled evaluations, likely to complete all required tests, and likely to be compliant.
9. Men and women of child-bearing potential with partners of child-bearing potential must agree to use highly effective contraception. For male patients, contraception should continue for 3 months after the last dose of investigational medicinal product (IMP, one spermatic cycle). For female patients, contraception should continue for 6 months after the last dose of IMP (one oocyte cycle).
10. Women of non-childbearing potential must be post-menopausal (the last menstrual period was at least 12 months ago, and follicle-stimulating hormone \[FSH\] at screening confirms post-menopausal status), or have no uterus, ovaries, or fallopian tubes (or have their fallopian tubes tied). All women must have a negative pregnancy test result before administration of test article. Women who are surgically sterile must provide documentation of the procedure by an operative report or by ultrasound.

Exclusion Criteria:

1. Atypical parkinsonism, including that due to drugs, metabolic disorders, encephalitis, cerebrovascular disease, normal pressure hydrocephalus, or other neurodegenerative disease.
2. Any history of intellectual disability or psychiatric disorders, including substance use disorders, according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, except a history of mild depression/anxiety that has been resolved for at least the past 3 months.
3. A positive answer to questions 3 through 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening.
4. A positive Hepatitis B surface antigen, Hepatitis C antibody, or Human Immunodeficiency Virus (HIV) antibody test at screening.
5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 1.5 times the upper limit of normal (ULN) at screening or between screening and first dose administration.
6. Received or used an investigational product (including placebo) or device within the following time period prior to day -1 in the current study: 90 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer).
7. Use of non-prescription drugs, vitamins, herbal, and dietary supplements which has potential to influence the mitochondrial function (such as coenzyme Q10, carnitine, creatine, lipoic acid and vitamin E) within 30 days prior to day -1.
8. Use of drugs which are strong inhibitors of CYP3A4 or CYP3A4 substrates with narrow therapeutic index within 30 days prior to day -1.
9. History of clinically significant sensitivity to any of the study medications, or components thereof or a history of drug or other allergies that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
10. Women with a positive pregnancy test, are lactating, or are planning to become pregnant during the study or within 6 months of the end of this study.
11. A history or presence of any disease, condition, or surgery likely to affect drug absorption, distribution, metabolism, or excretion. Patients with a history of cholecystectomy should be excluded.
12. A history or presence of a clinically significant hepatic, renal, gastrointestinal, cardiovascular, endocrine, pulmonary, ophthalmologic, immunologic, hematologic, dermatologic, or neurologic (other than PD) abnormality.
13. At screening, any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, in the judgement of the Investigator or Medical Monitor, may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy.
14. A clinically significant vital signs abnormality at screening or day -1. This includes, but is not limited to, the following, in the sitting position (3 measurements, each 5 minutes apart):

    1. systolic blood pressure (SBP) \< 90 or \>140 mmHg,
    2. diastolic blood pressure (DBP) \< 50 or \> 95 mmHg, or
    3. heart rate \< 45 or \> 100 beats per minute.
15. In the opinion of the Investigator or Medical Monitor, the patient is unlikely to comply with the protocol or is unsuitable for any reason, e.g., known issues with ability to swallow tablets.
16. Women of child-bearing potential (WOCBP), or men, who are unwilling or unable to use accepted methods of birth control for up to 6 months following study participation.

16\. Contraindications for undergoing an MRI.

Where this trial is running

Groningen

• CTC Netherlands BV — Groningen, Netherlands (Recruiting)

Study contacts

• Study coordinator: Nadir Ulu, MD, PhD

Conditions Parkinson's Disease; Phase 2; SUL-238; Mitochondrial function; Magnetic Resonance Spectroscopy; MRS