Prospective Pilot Trial to Address the Feasibility and Safety of Treatment With Oral Zinc in GNAO1 Associated Disorders
概览
- 阶段
- 2 期
- 干预措施
- Zinc Acetate Dihydrate
- 疾病 / 适应症
- GNAO1
- 发起方
- Children's University Hospital Cologne, Germany
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Feasibility of daily treatment with oral zinc in GNAO1 as assessed by diary.
- 状态
- 已完成
- 最后更新
- 2个月前
概览
简要总结
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.
研究者
Moritz Thiel, MD
Pediatrician in pediatric neurology
Children's University Hospital Cologne, Germany
入排标准
入选标准
- •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
排除标准
- •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 \<
- •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
研究组 & 干预措施
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.
干预措施: Zinc Acetate Dihydrate
结局指标
主要结局
Feasibility of daily treatment with oral zinc in GNAO1 as assessed by diary.
时间窗: From first visit at Inclusion to visit after 6 month
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.
Safety of daily administered zinc in GNAO1 as assessed by regular evaluation of the side effects
时间窗: From first visit at inclusion until last phone call after 7 month
To assess side effects: two phone calls are made and in each visit at site potential side effects are assessed.
Safety of daily administered zinc in GNAO1 as assessed by regular blood tests
时间窗: Blood analysis at baseline, after 3 and 6 month
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.
次要结局
- Changes in general behaviour assessed by diary.(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.(Compare first two weeks of treatment to two weeks before the end of the trial)
- 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 motor-skills assessed by Gross-motor function measure(Compare measure at baseline to visit after 3 and 6 month)
- Microbiome of stool assessed by regular analysis(Samples compared from baseline to samples collected 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 dyskinesia assessed by a movement log for parents/caregivers(Compare first two weeks of treatment to two weeks before the end of the trial)
- Changes in sleep assessed by diary for parents/caregivers(Compare first two weeks of treatment to two weeks before the end of the trial)
- Changes in seizure duration assessed by seizure log.(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 at baseline, after 3 and 6 month)