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| Name | Class |
|---|---|
| The Clinical Trials Centre Cologne | OTHER |
| University of Cologne | OTHER |
| University of Geneva, Switzerland | OTHER |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Level of motor-skills assessed by Gross-motor function measure | The Gross-motor function measure(GMFM-66) is a standardized test for gross motor function, carried out by a physiotherapist. Minimum value 0, maximum value 100; a higher score is a better outcome. | Compare measure at baseline to visit after 3 and 6 month |
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Inclusion Criteria:
GNAO1 associated neurological disorder, documented by either
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)
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:
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| Name | Affiliation | Role |
|---|---|---|
| Moritz Thiel, MD | Children's Hospital, University Hospital Cologne, University of Cologne | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital, University Hospital Cologne, University of Cologne | Cologne | 50937 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36206333 | Background | 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. | |
| 37225406 | 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. |
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Trial results will be published in a scientific journal and presented at national or international congresses. Publication of the results of the trial as a whole is intended. Anonymized individual patient data (IPD) can be made available on reasonable request to the PI after the results are published.
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Prospective single arm, open-label pilot trial
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| Change in quality of life score assessed by Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire for caregivers |
The CPCHILD questionnaire is a validated measure of health-related quality of life for children with severe disabilities and is evaluated 3 times in this trial. Parents/caregivers are asked to fill out the questionnaire. The CPCHILD currently consists of 37 items distributed among six sections representing the following domains:
|
| Compare measure at baseline to visit after 3 and 6 month |
| Level of Dystonia assessed by the Burke-Fahn-Marsden Dystonia Rating scale | The Burke-Fahn-Marsden Dystonia Rating Scale is a universally applied instrument for the quantitative assessment of dystonia in both children and adults. It is divided into movement score and disability score. Movement score minimum value 0, maximum value 120; a higher score is a worse outcome with more dystonia present. Disability score minimum value 0; maximum value 30; a higher score is a worse outcome with more disabilities due to dystonia. | Compare measure at baseline to visit after 3 and 6 month |
| Level of dyskinesia assessed by the Abnormal involuntary movement scale (AIMS) | The AIMS is a 12-item clinician-rated scale to assess severity of dyskinesias (specifically, orofacial movements and extremity and truncal movements) and will be assessed 3 times at each visit at site. The minimum score is 0 and the maximum score is 4 (severe). A higher score is a worse outcome showing higher level of dyskinesia. | Compare measure at baseline to visit after 3 and 6 month |
| Level of dyskinesia assessed by a movement log for parents/caregivers | Parents/caregivers are given a diary in which they are asked to document the hours per day which are disturbed by movement disorder and involuntary movements. | Compare first two weeks of treatment to two weeks before the end of the trial |
| Changes in sleep assessed by diary for parents/caregivers | Parents/Caregivers are asked to fill out a diary addressing time of sleep per day and sleep disturbances. | Compare first two weeks of treatment to two weeks before the end of the trial |
| Changes in general behaviour assessed by diary. | Parents/Caregivers are asked to fill out a diary addressing the general behaviour with two questions. | Compare answers of diary of first two weeks of treatment to two weeks before the end of the trial |
| Changes in seizure frequency assessed by seizure log. | Parents/Caregivers are requested to document frequency in a seizure log which is part of the diary | Compare first two weeks of treatment to two weeks before the end of the trial |
| Changes in seizure duration assessed by seizure log. | Parents/Caregivers are requested to document duration of seizures in a seizure log which is part of the diary | Compare first two weeks of treatment to two weeks before the end of the trial |
| Changes in serum level of zinc assessed by regular blood analysis | Serum controls of zinc are assessed three times to measure the changes in serum levels of zinc before and while zinc administration | Serum controls at baseline, after 3 and 6 month |
| Microbiome of stool assessed by regular analysis | Analyze of the microbiome in stool to detect changes under therapy with oral zinc.The stool samples should be collected at home in the three days before visit 2 and 3 in special sample tubes that are handed out to the patient at visit 0. The first stool samples should be collected at visit 0 or on the first three days thereafter. | Samples compared from baseline to samples collected after 3 and 6 month |
| 37956232 | 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/ |
| 33036271 | 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. |
| 40277885 | Derived | 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. |
| ID | Term |
|---|---|
| D004421 | Dystonia |
| D004827 | Epilepsy |
| D007859 | Learning Disabilities |
| ID | Term |
|---|---|
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D003147 | Communication Disorders |
| D019954 | Neurobehavioral Manifestations |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D019345 | Zinc Acetate |
| ID | Term |
|---|---|
| D019342 | Acetic Acid |
| D000085 | Acetates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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