Prospective Pilot Trial to Address Feasibility and Safety of Oral Zinc in GNAO1 Associated Disorders

NCT ID: NCT06412653

Last Updated: 2026-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-02
• Study Completion Date: 2025-08-04

Brief Summary

The goal of this clinical trial is to investigate feasibility and safety of an oral therapy with zinc in patients affected by Guanine nucleotide-binding protein G(o) subunit alpha (GNAO1) associated disorders.

The main questions it aims to answer are:

• Is a daily oral therapy with zinc in GNAO1 associated disorders a safe and feasible therapy?
• Are there potential changes in general motor skills, general behaviour and well being, day/night rhythm, level of dyskinesia and dystonia, frequency of seizures, quality of life and changes in the microbiome of the patients.

Participants with GNAO1 associated disorders will be given an oral zinc therapy for 6 month and will be assessed in 3 visits and 2 phone calls within this trial.

Conditions

GNAO1; Dystonia; Epilepsy; Development Delay; Developmental and Epileptic Encephalopathy 17; Neurodevelopmental Disorder With Involuntary Movements; Choreoathetosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Interventional Arm

Zinc acetate dihydrate in age-adapted dosage ranging from 50mg to 150mg Zn2+ per day according to the recommended dosage in Wilsons Disease.

Group Type: EXPERIMENTAL

Zinc Acetate Dihydrate

Intervention Type: DRUG

In this single arm trial, all participants will be receive the trial drug zinc acetate dihydrate orally. The Investigational medicinal product (IMP) will be given one hour after meal in a dosage which is recommended in Wilson Disease and has been given in this condition without observing severe adverse effects. If oral administration is not possible due to the disability level of the patient, the IMP can be mortared and suspended and can then be given as suspension orally or via the Percutaneous endoscopic gastrostomy. The total treatment duration in each patient is 6 months with stable dosage over the duration of the trial. If the therapy shows effects, the parents and participants may continue medication after the end of the trial. If not, they will stop the medication after the last visit at the trial site.

Interventions

Zinc Acetate Dihydrate

In this single arm trial, all participants will be receive the trial drug zinc acetate dihydrate orally. The Investigational medicinal product (IMP) will be given one hour after meal in a dosage which is recommended in Wilson Disease and has been given in this condition without observing severe adverse effects. If oral administration is not possible due to the disability level of the patient, the IMP can be mortared and suspended and can then be given as suspension orally or via the Percutaneous endoscopic gastrostomy. The total treatment duration in each patient is 6 months with stable dosage over the duration of the trial. If the therapy shows effects, the parents and participants may continue medication after the end of the trial. If not, they will stop the medication after the last visit at the trial site.

Intervention Type: DRUG

Other Intervention Names

WILZIN 25mg; WILZIN 50mg; Wilzin

Eligibility Criteria

Inclusion Criteria

• GNAO1 associated neurological disorder, documented by either

• Proven pathogenic or likely pathogenic mutation in GNAO1 or
• a variant of unknown significance in GNAO1 and clinical symptoms likely to be consistent with GNAO1 as determined by the investigators and
• at least one of the common symptoms of GNAO1: Movement disorder (Dystonia, Chorea, Ataxia, clonic), central muscular hypotonia, epilepsy, global developmental delay
• Age: 6 month - 30 years
• GMFM ≤ 75
• written informed consent prior to any trial-related procedure (according to age and status of psycho-intellectual development)

• of parents or legal guardian
• of parents or legal guardian and patient
• of the patient
• stable on following concomitant treatments for at least 3 months prior to trial inclusion: anti-seizure drugs (ASD); baclofen, Deep brain stimulation settings

Exclusion Criteria

• Treatment of Zinc in the last 4 months before inclusion
• known other genetic variants that are known to cause symptoms like observed in GNAO1-related disorders, additional to the proven GNAO1 mutation
• implantation of Deep brain stimulation planned during the duration of the trial, i.e. in the six months after inclusion
• start of intrathecal baclofen therapy planned during the duration of the trial, i.e. in the six months after inclusion
• Known allergy/hypersensitivity to the scheduled trial drug
• Concomitant participation in other clinical drugs with investigational drugs or with competing interventions
• sexually active patients who are not willing to use/ not using a highly effective contraception method with a pearl-index < 1. Sexually active patients, unless surgically sterile, must be using a highly effective contraception method (including oral, transdermal, injectable or implanted contraceptives, intrauterine device (IUD), using a condom of the sexual partner or sterile sexual partner) and must agree to continue using such precautions during the whole study period.
• Pregnant women and nursing mothers

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Clinical Trials Centre Cologne

OTHER

Sponsor Role: collaborator

University of Cologne

OTHER

Sponsor Role: collaborator

University of Geneva, Switzerland

OTHER

Sponsor Role: collaborator

Children's University Hospital Cologne, Germany

OTHER

Sponsor Role: lead

Responsible Party

Moritz Thiel, MD

Pediatrician in pediatric neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Moritz Thiel, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital, University Hospital Cologne, University of Cologne

Locations

Children's Hospital, University Hospital Cologne, University of Cologne

Cologne, , Germany

Countries

Germany

References

Larasati YA, Savitsky M, Koval A, Solis GP, Valnohova J, Katanaev VL. Restoration of the GTPase activity and cellular interactions of Galphao mutants by Zn2+ in GNAO1 encephalopathy models. Sci Adv. 2022 Oct 7;8(40):eabn9350. doi: 10.1126/sciadv.abn9350. Epub 2022 Oct 7.

Reference Type: BACKGROUND

PMID: 36206333 (View on PubMed)

Thiel M, Bamborschke D, Janzarik WG, Assmann B, Zittel S, Patzer S, Auhuber A, Opp J, Matzker E, Bevot A, Seeger J, van Baalen A, Stuve B, Brockmann K, Cirak S, Koy A. Genotype-phenotype correlation and treatment effects in young patients with GNAO1-associated disorders. J Neurol Neurosurg Psychiatry. 2023 Oct;94(10):806-815. doi: 10.1136/jnnp-2022-330261. Epub 2023 May 24.

Reference Type: BACKGROUND

PMID: 37225406 (View on PubMed)

Briere L, Thiel M, Sweetser DA, Koy A, Axeen E. GNAO1-Related Disorder. 2023 Nov 9. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK597155/

Reference Type: BACKGROUND

PMID: 37956232 (View on PubMed)

Savitsky M, Solis GP, Kryuchkov M, Katanaev VL. Humanization of Drosophila Galphao to Model GNAO1 Paediatric Encephalopathies. Biomedicines. 2020 Oct 6;8(10):395. doi: 10.3390/biomedicines8100395.

Reference Type: BACKGROUND

PMID: 33036271 (View on PubMed)

Larasati YA, Solis GP, Koval A, Korff C, Katanaev VL. A Personalized 14-3-3 Disease-Targeting Workflow Yields Repositioning Drug Candidates. Cells. 2025 Apr 8;14(8):559. doi: 10.3390/cells14080559.

Reference Type: DERIVED

PMID: 40277885 (View on PubMed)

Other Identifiers

Uni-Koeln-5275

Identifier Type: -

Identifier Source: org_study_id