Treatment of Mitochondrial Dysfunction in Rett Syndrome With Triheptanoin

NCT02696044 | Unknown Phase 2

• 1 other identifier: IRB00085194
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Rett Syndrome

Keywords

Gastrointestinal Disorders

Outcome Measures

Primary Outcomes (2)

• Change in Clinical Seizure Frequency

  The number of observable seizures recorded via caregiver-reported diary between Visit 2 and Visit 7 of treatment.

  Visit 2, Visit 7 (Up to 4 months)

• Change in Dystonia frequency

  The frequency of dystonic posturing present in each limb recorded via caregiver-reported diary on each day of treatment between Visit 2 and Visit 7 of treatment.

  Visit 2, Visit 7 (Up to 4 months)

Secondary Outcomes (27)

• Change in Dystonia Severity

  Visit 1, Visit 7 (Up to 4 months)

• Change in Burke-Fahn-Marsden Dystonia Rating Scale (BFM) Score

  Visit 1, Visit 9 (Up to 8.5 months)

• Change in Global Dystonia Rating Scale (GDRS) Score

  Visit 1, Visit 9 (Up to 8.5 months)

• Change in the PROMIS Fatigue Parent Proxy Score

  Visit 2, Visit 7 (Up to 4 months)

• Change in the PROMIS Pain Interference Parent Proxy Score

  Visit 2, Visit 7 (Up to 4 months)

Study Arms (6)

Participants aged 0 months to 3 years

EXPERIMENTAL

Participants will receive 4 grams of triheptanoin per kilogram of body weight daily.

Drug: triheptanoin

Participants aged 4 to 6 years

EXPERIMENTAL

Participants will receive 3 grams of triheptanoin per kilogram of body weight daily.

Drug: triheptanoin

Participants aged 7 to 9 years

EXPERIMENTAL

Participants will receive 2.5 grams of triheptanoin per kilogram of body weight daily.

Drug: triheptanoin

Participants aged 10 to 14 years

EXPERIMENTAL

Participants will receive 2 grams of triheptanoin per kilogram of body weight daily.

Drug: triheptanoin

Participants aged 15 to 20 years

EXPERIMENTAL

Participants will receive 1.5 grams of triheptanoin per kilogram of body weight daily.

Drug: triheptanoin

Participants aged 21 years and older

EXPERIMENTAL

Participants will receive 1.2 grams of triheptanoin per kilogram of body weight daily.

Drug: triheptanoin

Interventions

triheptanoin DRUG

Participants will begin a 2 week dose titration period to achieve study drug treatment comprising of 1-4 grams per kilogram of body weight (g/kg) daily depending on age. The age-related target dose will be mixed with food or formula and administered orally or by gastronomy tube. The total daily dose can be divided into 4 equal doses taken 4 times daily. Participants will maintain the age dependent dose treatment at the 1-4 g/kg daily for four months.

Participants aged 0 months to 3 years; Participants aged 10 to 14 years; Participants aged 15 to 20 years; Participants aged 21 years and older; Participants aged 4 to 6 years; Participants aged 7 to 9 years

Eligibility Criteria

• Age: 2 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Center for Rare Neurological Diseases, Norcross, GA: lead
• Ultragenyx Pharmaceutical Inc: collaborator
• Rett Syndrome Research Trust: collaborator

Study Sites (1)

Center for Rare Neurological Diseases

Norcross, Georgia, 30093, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 32165033 DERIVED

MeSH Terms

Conditions

Rett Syndrome; Gastrointestinal Diseases

Interventions

triheptanoin

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Digestive System Diseases

Study Officials

• Daniel Tarquinio, DO

  Center for Rare Neurological Diseases

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel Tarquinio, DO

CONTACT

207-590-6945; daniel@rareneuro.com

Jennifer Harris

CONTACT

770-315-2207; jennifer@rareneuro.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Managing Director

Study Record Dates

• First Submitted: February 25, 2016
• First Posted: March 2, 2016
• Study Start: June 1, 2016
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2022
• Last Updated: July 17, 2020

Record last verified: 2020-07

Locations

US (1)