Clinical Study of a Single Ciliopathy: Alström Syndrome

Sponsor

University Hospital, Strasbourg, France (Other)

Overall Status

Terminated

CT.gov ID

NCT02890550

Collaborator

(none)

Enrollment

Locations

48.1

Duration (Months)

5.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the study is to characterize the clinical manifestations of ALMS within the ciliopathies to prevent complications and determine preventive and therapeutic targets.

The investigators believe that the clinical consequences of mutations in the gene result ALMS1 unprecedented protests and the ALMS study should help to be informed, not only about the understanding and decision support other ciliopathies, but also about some common diseases, as some physiopathogenic roads could be common; the rare disease being exacerbated a model of the channel concerned. Secondarily, the clinical data generated by this project will also be used as part of basic research (eg comparison with results in animal models, use of human cells for in vitro studies or transcriptomic ....) (which will be a secondary upgrading to this work).

Condition or Disease	Intervention/Treatment	Phase
Alström Syndrome (ALMS)

Study Design

Study Type:

Observational

Actual Enrollment :

75 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Clinical Study of a Single Ciliopathy: Alström Syndrome

Study Start Date :

Apr 1, 2014

Actual Primary Completion Date :

Apr 5, 2018

Actual Study Completion Date :

Apr 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
30 Patients Alström syndrome
60 Related patients Alström syndrome

Outcome Measures

Primary Outcome Measures

Genetic Diagnosis [6 months]
In this project, 8 clinical research modules covering major medical issues goshawks ALMS (Genetic diagnosis, neurosensory infringement (ophthalmology and ENT (hearing and olfaction) and neuro-cognitive impairment), obesity & diabetes, endocrine achievement, nephrologic achievement, cardiological achievement, pneumologic achievement, reproductive biology). For each module, the current state of knowledge, clinical issues and their impact on the management of short and medium term ALMS patients are detailed. The clinical complications of this disease must be identified rationally and treatment and clinical management optimized on robust foundations for enhanced medical knowledge. The development of targeted therapies will depend on the clinical research data is the basic foundation of work which can then be enriched by the scientific data currently booming in this area.
Neurosensory infringement [6 months]
Ophtalmology study: consultation with visual acuity evaluation, examination at the slit lamp, intraocular pressure measurement, fundus examination, evaluation of Goldmann visual field, rétinophotography, standard and multifocal electroretinography, color vision, Optical Coherence Tomography (OCT), orthoptic balance proportion of initial macular involvement and impact on future therapeutic trials (eg retina / age thickness) consequences of low vision on posterior optical channels (including occipital cortex) Olfaction study: brushing the nasal mucosa, isotopic mucociliary clearance, olfactometry (test UPSIT) gustometry, audiogram, otoacoustic emissions, auditory evoked potentials Is the origin of deafness endocochlear only? OAS are they a predictive test and prognosis? Are ALMS patients suffering anosmia as for other ciliopathies? Mobile eyelashes respiratory mucosal abnormalities are they like other ciliopathies?
Neurocognitive impairment [6 months]
Neurocognitive explorations: Neuropsychological assessment with cognitive tests, psychiatric evaluation, MRI, to determine if ALMS patients have cognitive impairment. Validation of a second population of a new innovative battery of neurocognitive tests for the visually impaired.
Obesity - Diabetes [6 months]
Study of the origin of obesity: Origin central or peripheral obesity? Determinism of insulin resistance and diabetes? nutrition consultation, impedance, basal calorimetry and OGTT, food investigation over 3 days and dietary questionnaires, laboratory tests, calorimetry, polysomnography (Embletta), abdominal-pelvic MRI
Endocrine Achievement [6 months]
Endocrine study: - Determine the primary endocrine deficiencies of those who are secondary to obesity and metabolic disorders. OGTT, test LHRH
Nephrologic achievement [6 months]
Nephrology consultation including water deprivation test and renal ultrasound, to determine what is the primum movens at the renal impairment (glomerular or tubular origin), and if there is a particular component in fibrotic renal disease compared to other ciliopathies. nephrology consultation, water deprivation test, renal ultrasound
Cardiological achievement [6 months]
Study of cardiovascular risk factors: - Which patients have cardiac fibrosis? At what age and what connection with possible cardiomyopathy childhood? Cardiology consultation including echocardiogram, electrocardiogram (ECG), ambulatory blood pressure measurement, cardiac MRI, cardiac great vessels holter doppler
Pneumologic achievement [6 months]
Respiratory function study: Are respiratory alterations related to a breach of mobile eyelashes? Do ALMS patients develop respiratory fibrosis and in which context ? Spirometry, exhaled NO
Reproductive biology [6 months]
To explain infertility of ALMS patients (men or women)

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria for Patients with Alström syndrome:

Age> 2 years
Affiliated with a social security scheme
Informed consent signed
Retinal dystrophy and proved at least three diagnostic criteria Alström syndrome (Criteria Marshall et al, 2005):
Early obesity
Deafness
Dilated cardiomyopathy
Type 2 diabetes
Hypogonadism
Absence of polydactyly
Lack of mental retardation
A family history of the ALMS
Mutation in the ALMS gene identified

Inclusion Criteria for Related of Alström patients :

Father / Mother of a patient diagnosed with Alström
Age greater than 18 years
Affiliated with a social security scheme
Informed consent signed

Exclusion Criteria for Patients with Alström syndrome:

Current pregnancy (a pregnancy test is routinely performed at baseline)
Pregnant or breastfeeding women
Intercurrent diseases do not allow the practice exams in protocol
Subject to exclusion period (determined by a previous study or a study in progress)

Exclusion Criteria for Related of Alström patients :

Age less than 18 years
Subject to exclusion period (determined by a previous study or a study in progress)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CMCO, Hôpitaux Universitaires	Schiltigheim	France	67300
2	Centre d'Investigation Clinique, Nouvel Hôpital Civil, Hôpitaux Universitaires	Strasbourg	France	67091
3	Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpitaux Universitaires	Strasbourg	France	67091
4	Clinique Psychiatrique, Hôpital Civil, Hôpitaux Universitaires	Strasbourg	France	67091
5	Service de Cardiologie, Nouvel Hôpital Civil, Hôpitaux Universitaires	Strasbourg	France	67091
6	Service de néphrologie et hémodialyse, Hôpital Civil, Hôpitaux Universitaires	Strasbourg	France	67091
7	Service de physiologie et des Explorations Fonctionnelles, Nouvel Hôpital Civil, Hôpitaux Universitaires	Strasbourg	France	67091
8	Service de Psychothérapie pour Enfants et Adolescents, Hôpital Civil, Hôpitaux Universitaires	Strasbourg	France	67091
9	Service d'Imagerie 1, Hôpital de Hautepierre, Hôpitaux Universitaires	Strasbourg	France	67098
10	Service d'ORL et de Chirurgie Cervico-Faciale, Hôpital de Hautepierre, Hôpitaux Universitaires	Strasbourg	France	67098
11	Service de Génétique Médicale, Hôpital de Hautepierre, Hôpitaux Universitaires	Strasbourg	France	67098
12	Service de Médecine Interne, Endocrinologie et Nutrition, Hôpital de Hautepierre, Hôpitaux Universitaires	Strasbourg	France	67098
13	Service de Pédiatrie 1, Hôpital de Hautepierre, Hôpitaux Universitaires	Strasbourg	France	67098
14	Service de Radiologie 2, Hôpital de Hautepierre, Hôpitaux Universitaires	Strasbourg	France	67098

Sponsors and Collaborators

University Hospital, Strasbourg, France

Investigators

Principal Investigator: Hélène DOLLFUS, MD, Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpitaux Universitaires de Strasbourg