Clinical trial NCT02588638: Next Generation Sequencing Diagnostics - On the Road to Rapid Diagnostics for Rare Diseases
Official title: Next Generation Sequencing Diagnostics - On the Road to Rapid Diagnostics for Rare Diseases
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Movement Disorder
Cognitive Decline
Keywords: NGS
Quality of life
Diagnosis
Rare disease
Next-generation sequencing
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2015-10-28
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with unclear diagnoses

Brief summary: In the study, NextGen SE are on-hand a cohort comprising each 50 pediatric and 50 adult patients, and in which there are an unclear movement disorder or an unclear cognitive disorder, examines the following questions :

Primary:

* Number of diagnoses made by NGS

Secondary:

1. restriction of the quality of life by unclear disease
2. Cost of not purposeful preliminary diagnostics ( beyond the minimal diagnostic data set )
3. Impact of the diagnosis to therapy and follow-up examinations
4. Time to diagnosis

Detailed description: In the study NextGen SE (single-center, prospective, open diagnostic study) are on-hand a cohort comprising each 50 pediatric and 50 adult patients, and in which there are an unclear movement disorder or an unclear cognitive disorder, examines the following questions:

Primary:

* Number of diagnoses made by next-generation sequencing (NGS)

Secondary:

1. Restriction of the quality of life by unclear disease
2. Cost of not purposeful preliminary diagnostics (beyond the minimal diagnostic data of the diagnosis to therapy and follow-up examinations
3. Time to diagnosis

Eligibility criteria: Inclusion Criteria:

For patients\> 18 years

1. Unclear movement disorder

   o Progressive ataxia after minimal exclusion diagnostics: magnetic resonance tomography (MRT) (structural lesions such as cerebellar tumor, malformation) Laboratory (Vitamin B12, thyroid peroxidase (TPO) antibodies, glutamate decarboxylase (GAD) II-antibodies (AK) In medullary lesions: Liquor exclusion Friedreich ataxia (FRDA) and spinocerebellar ataxia type (SCA)1-2-3-6

   o Progressive para-spasticity by minimal exclusion diagnostics: MRT neuro axis (structural lesions such as cervical myelopathy) Laboratory (Vitamin B12, human T-cell lymphotrophic virus ((HTLV)-AK) In medullary lesions: Liquor
2. Unclear cognitive decline o After minimal exclusion diagnosis MRT (intracranial pressure, focal brain lesions explanatory) laboratory (Thyroid-stimulating hormone (TSH), TPO-AK, antibody profile limbic encephalitis) Liquor (inflammation, meningitis) Electroencephalography (EEG) (Status) Exclusion chromosome 9 open reading frame 72 (C9orf72)

For patients \<18 years Patients with (penetrating) suspected cerebral neurogenetic diseases

* Unclear movement disorder (spasticity, ataxia, dyskinesia)
* Unclear cognitive disorder with probability of monogenic origin
* Fragile X Syndrome (Fra-X) at mentally retarded boy, Friedreich ataxia (FRDA) with ataxia should be genetically excluded

Exclusion Criteria:

For patients \> 18 years

1. Lack of consent
2. symptom onset \> 40 years of age
3. Sudden, abrupt beginning
4. As early as previous history of genetic diagnosis using next-generation sequencing (NGS), also in the form of a panel

For patients \<18 years

1. injury brain disorders

   * On the basis of imaging
   * On the basis of medical history (premature baby, hypoxic-ischemic encephalopathy)
2. Inflammatory brain disorders

   * On the basis of imaging
   * On the basis of laboratory parameters (Oligoclonal fractions, cerebrospinal fluid (CSF) cell count increased)
3. Light, isolated mental developmental disorder or behavioral disorder (rare monogenetic) - (less than 2 standard deviartion of normal or - \< 6 year olds - less than 1 year in development history back)
4. Sudden , abrupt beginning
5. Next-generation sequencing (NGS) also in the form of a panel

Primary outcomes:
measure: Number of diagnoses made by next gereration sequency (NGS)
timeFrame: Within the study period of 18 months
Secondary outcomes:
measure: Restriction of the quality of life by unclear disease measured rated by Quality of Life Questionnaire (EQ5D), Depression Questionnaire (PHQ)
timeFrame: At day 1
measure: Cost of not purposeful preliminary diagnostics rated by questionnaire on costs (number of outpatient performances, stationary investigations, repetition 's imaging, genetic single diagnostics, high-priced diagnostic
timeFrame: At day 1
measure: Time to diagnosis
timeFrame: At day 1
Other outcomes:
Locations:
city: Tubingen
country: Germany
facility: University Hospital
state: Baden-Württemberg
Study officials:
affiliation: University Hospital Tübingen
name: Ludger Schöls, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: