Clinical trial NCT02696044: Treatment of Mitochondrial Dysfunction in Rett Syndrome With Triheptanoin
Official title: Treatment of Mitochondrial Dysfunction in Rett Syndrome With Triheptanoin: An Open-label, 10-subject Clinical Trial of UX007 (Triheptanoin) in the Treatment of Mitochondrial Dysfunction in Participants With Rett Syndrome, Dyskinesia, and Epilepsy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rett Syndrome
Keywords: Gastrointestinal Disorders
Lead sponsor: Center for Rare Neurological Diseases, Norcross, GA
Sponsor class: OTHER
Collaborators: name: Ultragenyx Pharmaceutical Inc
name: Rett Syndrome Research Trust
First posted: 2016-03-02
Enrollment: 12
Sex: FEMALE
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the safety and tolerability of triheptanoin in participants with Rett syndrome using laboratory values, electrocardiogram, rate of adverse events (AE), and physical exam.This study also seeks to evaluate the efficacy of UX007 (triheptanoin) in improving overall seizure frequency and dystonia.

Detailed description: The aim of this study is to evaluate the safety and tolerability of triheptanoin in participants with Rett syndrome using laboratory values, electrocardiogram, rate of adverse events (AE), and physical exam. This study also seeks to evaluate the efficacy of UX007 (triheptanoin) in improving overall seizure frequency, dystonia severity, and quality of life. Participants who are eligible will take triheptanoin daily. Participation in the primary arm of this study will last up to 8.5 months, with an optional 36 month extension.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Classic Rett syndrome as defined by the clinical consensus criteria
* Presence of a MECP2 mutation
* Post-regression stage of development, defined as greater than 6 months since the last loss of hand use or verbal language
* Average of at least 4 observable seizures (generalized or partial-onset \[Generalized Tonic-Clonic, Generalized Tonic, Generalized Clonic, Generalized Atonic, Partial/Focal with Secondary Generalization, Myoclonic, Myoclonic Atonic, Myoclonic Tonic, Complex Partial/Focal, and Simple Partial/Focal Motor) in one month prior to the study by caregiver report or presence of dystonia on average at least four times in one month prior to the study in at least one body region rated as at least "mild" by caregiver report
* Use of at least one anti-seizure medication at screening visit
* At screening visit, managed on four or fewer concomitant anti-seizure medications that must have been stable in dose at least one month prior to the beginning of screening and anticipated to remain stable in dose through the end of the 8.5 month trial period
* Legally authorized caregiver must be willing to give written informed consent after the nature of the study has been explained, and prior to any research-related procedures
* Caregiver and participant must, in the opinion of the investigator, be willing and able to complete all aspects of the study, comply with accurate completion of the seizure and dystonia diaries, and be likely to complete the four month treatment period

Exclusion Criteria:

* Markedly abnormal metabolic screening laboratory testing (e.g., serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2X the upper limit of normal)
* Any known hypersensitivity to triheptanoin that, in the judgment of the investigator, places the subject at increased risk for adverse effects
* Prior use of triheptanoin within 1 month prior to screening
* Participants or caregivers who are unwilling or unable to discontinue use of a prohibited medication or other substance that may confound study objectives
* Use of any other investigational product, including drugs or supplements within 1 month prior to Screening, or at any time during the study
* Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment
* Has a concurrent disease or condition, or laboratory abnormality that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or introduces additional safety concerns (e.g., diabetes mellitus)
* Pregnant or nursing women

Primary outcomes:
measure: Change in Clinical Seizure Frequency
timeFrame: Visit 2, Visit 7 (Up to 4 months)
measure: Change in Dystonia frequency
timeFrame: Visit 2, Visit 7 (Up to 4 months)
Secondary outcomes:
measure: Change in Dystonia Severity
timeFrame: Visit 1, Visit 7 (Up to 4 months)
measure: Change in Burke-Fahn-Marsden Dystonia Rating Scale (BFM) Score
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Change in Global Dystonia Rating Scale (GDRS) Score
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Change in the PROMIS Fatigue Parent Proxy Score
timeFrame: Visit 2, Visit 7 (Up to 4 months)
measure: Change in the PROMIS Pain Interference Parent Proxy Score
timeFrame: Visit 2, Visit 7 (Up to 4 months)
measure: Change in the PROMIS Peer Relations Parent Proxy Score
timeFrame: Visit 2, Visit 7 (Up to 4 months)
measure: Change in the PROMIS Physical Functional Mobility Parent Proxy Score
timeFrame: Visit 2, Visit 7 (Up to 4 months)
measure: Change in the PROMIS Physical Function Upper Extremity Parent Proxy Score
timeFrame: Visit 2, Visit 7 (Up to 4 months)
measure: Change in the PROMIS Anxiety Parent Proxy Score
timeFrame: Visit 2, Visit 7 (Up to 4 months)
measure: Change in the PROMIS Depressive Symptoms Parent Proxy Score
timeFrame: Visit 2, Visit 7 (Up to 4 months)
measure: Change in Child Health Questionnaire-50 (CHQ) Score
timeFrame: Visit 2, Visit 7 (Up to 4 months)
measure: Change in the Clinician Clinical Global Impression - Improvement Scale (CGI-S) Score
timeFrame: Visit 2, Visit 9 (Up to 8.5 months)
measure: Change in the Clinician Clinical Global Impression - Severity Scale Score
timeFrame: Visit 2, Visit 9 (Up to 8.5 months)
measure: Change in the Parental Clinical Global Impression of Improvement Score
timeFrame: Visit 2, Visit 9 (Up to 8.5 months)
measure: Change in Parent Top Three Concerns Visual Analog Scale Ranking
timeFrame: Visit 2, Visit 9 (Up to 8.5 months)
measure: Change in the Clinical Severity Scale (CSS) Score
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Change in the Motor Behavioral Assessment (MBA) Score
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Change in the Rett Syndrome Behavioural Questionnaire (RSBQ) Score
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Change in the Rett Syndrome Hand Apraxia Scale (RHAS) Score
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Change in the Rett Syndrome Gross Motor Scale (RSGMS) Score
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Change in Maximum Heart Rate as assessed by the Graded Maximal Treadmill Test
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Change in Maximum Speed Acheived as assessed by the Graded Maximal Treadmill Test
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Frequency of Epileptiform Electroencephalogram (EEG) Activity
timeFrame: Visit 1, Visit 7 (Up to 6.5 months)
measure: Seizure Activity assessed by Change in Photoplethysmographic Heart Rate
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Change in Daily 3-axis accelerometry
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Seizure Activity assessed by Change in Electrodermal Activity (EDA)
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
measure: Seizure Activity assessed by Change in Skin Temperature
timeFrame: Visit 1, Visit 9 (Up to 8.5 months)
Other outcomes:
Locations:
city: Norcross
country: United States
facility: Center for Rare Neurological Diseases
state: Georgia
Study officials:
affiliation: Center for Rare Neurological Diseases
name: Daniel Tarquinio, DO
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hou W, Bhattacharya U, Pradana WA, Tarquinio DC. Assessment of a Clinical Trial Metric for Rett Syndrome: Critical Analysis of the Rett Syndrome Behavioural Questionnaire. Pediatr Neurol. 2020 Jun;107:48-56. doi: 10.1016/j.pediatrneurol.2020.01.009. Epub 2020 Feb 4.