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

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.

Study Overview

• Status: Completed
• Conditions: Familial Fatal Insomnia
• Intervention / Treatment: Drug: Doxycycline Hcl; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 44 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborators: Fondazione Telethon

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2011
• Primary Completion (Actual): April 12, 2021
• Study Completion (Actual): April 12, 2021

Study Registration Dates

• First Submitted: April 12, 2021
• First Submitted That Met QC Criteria: April 12, 2021
• First Posted (Actual): April 15, 2021

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Central Nervous System Diseases; Nervous System Diseases; Infections; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Central Nervous System Infections; Neurodegenerative Diseases; Prion Diseases; Sleep Initiation and Maintenance Disorders; Insomnia, Fatal Familial; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: FFI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No