Familiar Fatal Insomnia: Preventive Treatment With Doxycycline in Subject With Disease Risk

Study Overview
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Brief Summary
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The neurodegenerative disorders is a class o pathologies including very common diseases as Alzheimer or Parkinson or very rare as fatal familial insomnia (FFI), the progression of the disease with no therapeutic remedy is the common tract of these disorders. The aim of this project is to carry out a preventive treatment in subjects with genetic risk to develop FFI to avoid the establishment of the disease. FFI is a rare genetic neurodegenerative disease characterized by disrupted sleep, autonomic hyperactivation and motor abnormalities with fatal exitus. FFI is inherited in an autosomal dominant fashion and is linked to the D178N mutation in the prion protein gene (PRNP) in association with a methionine at the polymorphic codon 129 (D178N/M129). About thirty FFI pedigrees have been described worldwide, the mfirst case being reported in 1986 in northern Italy. This patient turned out to belong to large kindred, which spans 7 generations dating back to the eighteenth century. Many people belonging to this geneaology still live in the Veneto region of Italy, and they are part of an association. The genetic screening of 85 subjects belonging to this family permitted to identify the mutation carriers. Since the disease is aggressive and the affected people usually died within thirteen months from the onset, the possibility of an efficacious therapy when the disease become evident is unrealistic. This condition indicates in a preventive approach the better condition to affect the disease. Experimental studies and clinical observation indicated the antibiotic doxycycline (DOXY) as a potential candidate for a treatment in FFI subjects. The age with maximal risk to get the disease is between 50 and 55 years old. Thus the carriers that were born between 1958 and 1969 will be recruited for a preventive treatment with DOXY for ten years, at the end of this period or before we can establish if DOXY can be useful to avoid the development of FFI.

Official Title
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Familiar Fatal Insomnia: Preventive Treatment With Doxycycline in Subject With Disease Risk

Conditions
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Familial Fatal Insomnia

Intervention / Treatment
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* Drug: Doxycycline Hcl
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects aged 44 to 53 years; no conditions known to be contraindications to the use of tetracyclines; written informed consent. Exclusion Criteria: end stage liver, heart and renal disease, active malignancy, female subjects who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 44 Years
Maximum Age: 53 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Bassado<br>patients with D178N/M129 mutation on prion protein will be treated with Bassad | Drug: Doxycycline Hcl<br>* tablets of DOXY hydrocloride (Bassado)<br>|
| Placebo Comparator: Placebo<br>subject without the mutation will be treated with plac | Drug: Placebo<br>* tablets of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival | The efficacy of the preventive treatment will be evaluated on the percentage of the survivals after ten years, according to the statistical analysis if no more than three individuals will die within the ten years, the treatment can be considered active to prevent FFI insurgence. | after 10 years of treatment |