Therapeutic Metabolic Intervention in Patients With Spastic Paraplegia SPG5

Phase 2

Completed

• Conditions: Spastic Paraplegia, Hereditary
• Interventions: Dietary Supplement: Resveratrol; Drug: Xenbilox; Drug: Tahor

• Registration Number: NCT02314208
• Lead Sponsor: Institut National de la Santé Et de la Recherche Médicale, France

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

Study Timeline

• Study First Submitted: 2014-11-14
• Study First Submitted QC: 2014-12-10
• Study First Posted: 2014-12-11
• Study Start: 2015-01-08
• Primary Completion: 2017-09-27
• Study Completion: 2018-01-01
• Status Verified: 2025-02
• Last Update Submitted: 2025-08-25
• Last Update Posted: 2025-09-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Resveratrol	Resveratrol	Resveratrol 80mg capsule by mouth every day for 2 months
Xenbilox	Xenbilox	Xenbilox (chenodeoxycholic acid) 1000mg capsule by mouth every day for 2 months
Tahor	Tahor	Tahor (atorvastatin) 40mg tablet by mouth every day for 2 months

Primary Outcome Measures

Name	Time	Method
Change of 27-hydroxycholesterol blood level after 2 months of treatment for each treatment	2 months	27-hydroxycholesterol will be measured on fasten blood samples for the 12 patients included before and after the 2-month treatment period for each treatment

Secondary Outcome Measures

Name	Time	Method
Number of partcipants with adverse events related with standard biological parameters	18 months	Biological tolerance will be evaluate on patients blood samples at each visit. The following criteria will be assessed: * ionogram and fasting glucose; * kidney and liver function with urea, creatinine,lipase, amylase, bilirubine, creatine phosphokinase, transaminases,sodium, potassium, calcium, phosphorus
Change of 25-hydroxycholesterol blood level after 2 months of treatment for each treatment	2 months	25-hydroxycholesterol will be measured on fasten blood samples for the 12 patients included before and after the 2-month treatment period for each treatment
Modification of the serum acid profile after a 2-month treatment measured in blood and urine samples	2 months	In blood and urines samples of the 12 patients, the following criteria will be assesed in order to observe an evolution of the acid profile: * total biliary acids; * ratio of primary/secondary biliary acids; * the ratio cholic acids/chenodeoxycholic acids; * the ratio chenodeoxycholic acids/ lithocholic acids
Number of participants with adverse events related with digestive problems	18 months	During the study, adverse events related with digestive problems will be evaluate in order to asses the clinical tolerance to each treatment

Trial Locations

Locations (1)

Pitié-Salpêtrière Hospital; 🇫🇷 Paris, France