Clinical Study of a Single Ciliopathy: Alström Syndrome

June 20, 2019 updated by: University Hospital, Strasbourg, France

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).

Study Overview

Status

Terminated

Conditions

Study Type

Observational

Enrollment (Actual)

75

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Schiltigheim, France, 67300
        • CMCO, Hôpitaux Universitaires
      • Strasbourg, France, 67091
        • Centre d'Investigation Clinique, Nouvel Hôpital Civil, Hôpitaux Universitaires
      • Strasbourg, France, 67091
        • Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpitaux Universitaires
      • Strasbourg, France, 67091
        • Clinique Psychiatrique, Hôpital Civil, Hôpitaux Universitaires
      • Strasbourg, France, 67091
        • Service de Cardiologie, Nouvel Hôpital Civil, Hôpitaux Universitaires
      • Strasbourg, France, 67091
        • Service de néphrologie et hémodialyse, Hôpital Civil, Hôpitaux Universitaires
      • Strasbourg, France, 67091
        • Service de physiologie et des Explorations Fonctionnelles, Nouvel Hôpital Civil, Hôpitaux Universitaires
      • Strasbourg, France, 67091
        • Service de Psychothérapie pour Enfants et Adolescents, Hôpital Civil, Hôpitaux Universitaires
      • Strasbourg, France, 67098
        • Service d'Imagerie 1, Hôpital de Hautepierre, Hôpitaux Universitaires
      • Strasbourg, France, 67098
        • Service d'ORL et de Chirurgie Cervico-Faciale, Hôpital de Hautepierre, Hôpitaux Universitaires
      • Strasbourg, France, 67098
        • Service de Génétique Médicale, Hôpital de Hautepierre, Hôpitaux Universitaires
      • Strasbourg, France, 67098
        • Service de Médecine Interne, Endocrinologie et Nutrition, Hôpital de Hautepierre, Hôpitaux Universitaires
      • Strasbourg, France, 67098
        • Service de Pédiatrie 1, Hôpital de Hautepierre, Hôpitaux Universitaires
      • Strasbourg, France, 67098
        • Service de Radiologie 2, Hôpital de Hautepierre, Hôpitaux Universitaires

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

7 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients will be recruited through the investigators' consultation Reference Center for Rare Diseases in Ophthalmological Genetics (CARGO) or sent by their colleagues from other cities including through very geneticists genetic Group or 3rd Thursdays ophthalmologists colleagues. Prior consultation CARGO will disclose the medical records of the intention of the patient to participate in this research (source document).

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
30 Patients Alström syndrome
60 Related patients Alström syndrome

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic Diagnosis
Time Frame: 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.
6 months
Neurosensory infringement
Time Frame: 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?
6 months
Neurocognitive impairment
Time Frame: 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.
6 months
Obesity - Diabetes
Time Frame: 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
6 months
Endocrine Achievement
Time Frame: 6 months

Endocrine study:

- Determine the primary endocrine deficiencies of those who are secondary to obesity and metabolic disorders.

OGTT, test LHRH
6 months
Nephrologic achievement
Time Frame: 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
6 months
Cardiological achievement
Time Frame: 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
6 months
Pneumologic achievement
Time Frame: 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
6 months
Reproductive biology
Time Frame: 6 months
To explain infertility of ALMS patients (men or women)
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2014

Primary Completion (Actual)

April 5, 2018

Study Completion (Actual)

April 5, 2018

Study Registration Dates

First Submitted

August 19, 2016

First Submitted That Met QC Criteria

August 31, 2016

First Posted (Estimate)

September 7, 2016

Study Record Updates

Last Update Posted (Actual)

June 21, 2019

Last Update Submitted That Met QC Criteria

June 20, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5514

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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