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

NCT06412653 | Completed Phase 2 DMC

• 1 other identifier: Uni-Koeln-5275
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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

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

Keywords

GNAO1

Outcome Measures

Primary Outcomes (3)

• Feasibility of daily treatment with oral zinc in GNAO1 as assessed by diary.

  The feasibility is measured by the actual days that zinc was taken in the right dosage. If zinc was taken in the scheduled dosage at least on 80% of the days it is assumed to be feasible. Parents/caregivers document the daily intake into a diary.

  From first visit at Inclusion to visit after 6 month

• Safety of daily administered zinc in GNAO1 as assessed by regular evaluation of the side effects

  To assess side effects: two phone calls are made and in each visit at site potential side effects are assessed.

  From first visit at inclusion until last phone call after 7 month

• Safety of daily administered zinc in GNAO1 as assessed by regular blood tests

  Serum ferritin and copper detect potential deficiencies, caused by regular zinc administration and therefore reduced uptake. Liver enzymes, alkaline phosphates, lipase and amylase are assessed 3 times, since these parameters can be elevated as side effect.

  Blood analysis at baseline, after 3 and 6 month

Secondary Outcomes (11)

• Level of motor-skills assessed by Gross-motor function measure

  Compare measure at baseline to visit after 3 and 6 month

• Change in quality of life score assessed by Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire for caregivers

  Compare measure at baseline to visit after 3 and 6 month

• Level of Dystonia assessed by the Burke-Fahn-Marsden Dystonia Rating scale

  Compare measure at baseline to visit after 3 and 6 month

• Level of dyskinesia assessed by the Abnormal involuntary movement scale (AIMS)

  Compare measure at baseline to visit after 3 and 6 month

• Level of dyskinesia assessed by a movement log for parents/caregivers

  Compare first two weeks of treatment to two weeks before the end of the trial

Study Arms (1)

Interventional Arm

EXPERIMENTAL

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

Drug: Zinc Acetate Dihydrate

Interventions

Zinc Acetate Dihydrate 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.

Also known as: WILZIN 25mg, WILZIN 50mg, Wilzin

Interventional Arm

Eligibility Criteria

• Age: 6 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• known other genetic variants that are known to cause symptoms like observed in GNAO1-related disorders, additional to the proven GNAO1 mutation
• 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

Sponsors & Collaborators

• University of Cologne: collaborator
• Children's University Hospital Cologne, Germany: lead
• The Clinical Trials Centre Cologne: collaborator
• University of Geneva, Switzerland: collaborator

Study Sites (1)

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

Cologne, 50937, Germany

Location

Related Publications (5)

• 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.

  PMID: 36206333 BACKGROUND

• 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.

  PMID: 37225406 BACKGROUND

• 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/

  PMID: 37956232 BACKGROUND

• 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.

  PMID: 33036271 BACKGROUND

• 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.

  PMID: 40277885 DERIVED

MeSH Terms

Conditions

Dystonia; Epilepsy; Learning Disabilities

Interventions

Zinc Acetate

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases; Communication Disorders; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Acetic Acid; Acetates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Moritz Thiel, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatrician in pediatric neurology

Model Details: Prospective single arm, open-label pilot trial

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: May 14, 2024
• Study Start: August 2, 2024
• Primary Completion: August 4, 2025
• Study Completion: August 4, 2025
• Last Updated: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)