NCT04846335: FFI

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

Completed Phase 2 Last updated 5 December 2024

What this trial tests

Phase 2 trial testing Doxycycline Hcl in Familial Fatal Insomnia in 29 participants. Completed in 30 November 2024.

Timeline

28 April 2011

Primary endpoint
12 April 2021

30 November 2024

Quick facts

Lead sponsor	Mario Negri Institute for Pharmacological Research
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	29
Start date	28 April 2011
Primary completion	12 April 2021
Estimated completion	30 November 2024

Drugs / interventions tested

• Doxycycline Hcl
• Placebo

Conditions studied

• Familial Fatal Insomnia — all drugs for Familial Fatal Insomnia →

Sponsor

Mario Negri Institute for Pharmacological Research

Who can join

Adults 44 to 53, any sex, with Familial Fatal Insomnia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Bridging the computational-experimental gap: leveraging large language model to prioritize Alzheimer's therapeutics based on comparison of learning models.
   Li M, Niu S, Xu Y, Li J, et al · · 2026 · PMID 41768541 · DOI 10.1038/s44401-026-00074-3