Clinical trial NCT02314208: Therapeutic Metabolic Intervention in Patients With Spastic Paraplegia SPG5
Official title: Therapeutic Metabolic Intervention in Patients With Spastic Paraplegia SPG5
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Spastic Paraplegia, Hereditary
Keywords: spastic paraplegia
metabolism
oxysterols
neurogenetics
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2014-12-11
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this project is to study the efficacy of three candidate molecules (Xenbilox, Tahor and Resveratrol) in order to decrease the production of oxysterols by reducing the synthesis of cholesterol and/or regulate the production of bile acids and/or enabling neuroprotective action within the motor neuron.

Detailed description: The primary objective of the study is:

- decrease the accumulation of metabolites which can have a negative impact on neurological and systemic function of patients with SPG5.

The secondary objectives of the study are:

* confirm the clinical and biological tolerance of the different candidate molecules under study
* improve the serum bile acid profile of patients with SPG5

Eligibility criteria: Inclusion Criteria:

* patients that have confirmed through genetic testing their status as carriers of 2 mutations in the CYP7B1 gene
* age ≥ 18 years
* patients that have signed the informed consent form
* presence of health care coverage

Exclusion Criteria:

* known hypersensitvity to chenodeoxycholic acid, atorvastatin, resveratrol or to any of their byproducts
* cholesterol lowering medications other than the study treatment
* hepatic failure with transaminases \>3 times the normal level
* progressive biliary pathology
* chronic diarrhea
* serious mental illness
* significant comorbid neurological disorder
* incapacity to understand information about the protocol
* unwilling or unable to participate in any part of the study
* participation in another clinical trial during the study period
* person deprived of liberty by judicial or administrative decision
* adult subject under legal protection or unable to consent
* pregnant or breastfeeding women
* lack of health care coverage
* absence of a signed informed consent form

Primary outcomes:
measure: Change of 27-hydroxycholesterol blood level after 2 months of treatment for each treatment
timeFrame: 2 months
Secondary outcomes:
measure: Modification of the serum acid profile after a 2-month treatment measured in blood and urine samples
timeFrame: 2 months
measure: Change of 25-hydroxycholesterol blood level after 2 months of treatment for each treatment
timeFrame: 2 months
measure: Number of participants with adverse events related with digestive problems
timeFrame: 18 months
measure: Number of partcipants with adverse events related with standard biological parameters
timeFrame: 18 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Pitié-Salpêtrière Hospital
Study officials:
affiliation: Pitié-Salpêtrière Hospital
name: Fanny MOCHEL, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: