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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
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.
Children's Hospital, University Hospital Cologne, University of Cologne
Cologne, Germany
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.
Time frame: 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.
Time frame: 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.
Time frame: Blood analysis at baseline, after 3 and 6 month
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.
Time frame: 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
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: 1. Activities of daily living/personal care (nine items) 2. Positioning, transferring and mobility (eight items) 3. Comfort and emotions (nine items) 4. Communication and social interaction (seven items) 5. Health (three items) 6. Overall quality of life (one item) In Section 7, caregivers rate the importance of each of these items' contribution to their child's quality of life.Scores for each domain and for the total survey are standardized and range from a minimum: 0 (worse) to a maximum 100 (best). A higher score is a better outcome.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: Samples compared from baseline to samples collected after 3 and 6 month
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