Clinical Study on the Safety of CNT-02 for TGCV and NLSD-M

Clinical Study on the Safety and Efficacy of Medium-chain Fatty Acid Capsules (CNT-02) for Primary Triglyceride Deposit Cardiomyovasculopathy (TGCV) and Neutral Lipid Storage Disease With Myopathy (NLSD-M)

This study is planning to evaluate the safety and clinical efficacy of medium-chain fatty acid capsules (food-grade CNT-02) in subjects with primary triglyceride deposit cardiomyovasculopathy (TGCV) and neutral lipid storage disease with myopathy (NLSD-M) associated with adipose triglyceride lipase (ATGL) genetic defects.

Study Overview

• Status: Terminated
• Conditions: Primary Triglyceride Deposit Cardiomyovasculopathy (TGCV); Neutral Lipid Storage Disease With Myopathy (NLSD-M)
• Intervention / Treatment: Dietary supplement: CNT-02

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Lazio
    • Rome, Lazio, Italy, 00163
      • IRCCS San Raffaele
    • Rome, Lazio, Italy, 00193
      • San Filippo Neri Hospital
  • Lombardia
    • Milano, Lombardia, Italy, 20123
      • Catholic University
  • Venice
    • Lido, Venice, Italy, 30126
      • Fondazione Ospedale San Camillo IRCCS
• Japan
  • Aomori-prefecture
    • Aomori-city, Aomori-prefecture, Japan, 030-8553
      • Aomori Prefectural Chuo Hospital
  • Miyagi-prefecture
    • Sendai-city, Miyagi-prefecture, Japan, 980-8575
      • Tohoku University
  • Osaka-prefecture
    • Suita-city, Osaka-prefecture, Japan, 565-0874
      • Graduate School of Osaka University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients for whom ATGL gene deletion has been previously confirmed.
2. Patients who can take the investigational product orally.
3. Male and female who are at least 20 years old at the time of consent.
4. Patients who gave written informed consent.

Exclusion Criteria:

1. Patients with diabetic ketoacidosis.
2. Patients with the possibility of diabetic ketoacidosis (patients with poorly controlled diabetes mellitus [HbA1c>8.4%, NGSP])
3. Patients with terminal malignancy.
4. Pregnant or lactating women.
5. Patients who do not consent to using contraception while participating in this study.
6. Patients allergic to MCT oil.
7. Patients participating in other clinical trial.
8. Otherwise, patients determined to be ineligible for this study by the investigator or sub-investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medium-chain Fatty Acid (CNT-02)	Dietary supplement: CNT-02; Each subject will take 2.0g of the investigational product orally 3 times a day after every meal. Unless an apparent worsening of symptoms or unacceptable adverse event occurs, the subject will continue to take the investigational product for up to 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The maximum walking distance in a 6-minute walk test at 3 months	Measuring maximum walking distance of 6-minute walk test. Calculating variation of those measured values from baseline to 3 months.	3 months
The maximum walking distance in a 6-minute walk test at 6 months	Measuring maximum walking distance of 6-minute walk test . Calculating variation of those measured values from baseline to 6 months.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRC sum score in manual muscle testing (MMT) at 3 months	Evaluating muscle strength by manual muscle test used MRC score. Assessing change from baseline to 3 months.	3 months
MRC sum score in manual muscle testing (MMT) at 6 months	Evaluating muscle strength by manual muscle test used MRC score. Assessing change from baseline to 6 months.	6 months
Fractions of lung volume such as % vital capacity, measured by spirometer at 3 months	Evaluating the respiratory functions by % Vital capacity measured by spirometer. Assessing change from baseline to 3 months.	3 months
Fractions of lung volume such as % vital capacity, measured by spirometer at 6 months	Evaluating the respiratory functions by % Vital capacity measured by spirometer. Assessing change from baseline to 6 months.	6 months
The amount of fat measured by computed tomography (CT) of the skeletal muscle (fat deposition) at 3 months	Evaluating fat deposition in the skeletal muscle by CT. Assessing change from baseline to 3 months.	3 months
The amount of fat measured by computed tomography (CT) of the skeletal muscle (fat deposition) at 6 months	Evaluating fat deposition in the skeletal muscle by CT. Assessing change from baseline to 6 months.	6 months
Parameters of cardiac function, such as the left ventricular ejection fraction by echocardiography at 3 months	Evaluating cardiac function using Left ventricular ejection fraction etc. by echocardiography. Assessing change from baseline to 3 months.	3 months
Parameters of cardiac function, such as the left ventricular ejection fraction by echocardiography at 6 months	Evaluating cardiac function using Left ventricular ejection fraction etc. by echocardiography. Assessing change from baseline to 6 months.	6 months
Serum free fatty acid levels at 3 months	Analysing concentration of fatty acids in serum using HPLC method. Assessing change from baseline to 3 months.	3 months
Serum free fatty acid levels at 6 months	Analysing concentration of fatty acids in serum using HPLC method. Assessing change from baseline to 6 months.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity, seriousness, causality, and outcomes of adverse events	A frequency counting of the adverse events. LLT code will be assigned to the reported adverse event using the MedDRA dictionary.	6 months

Collaborators and Investigators

• Sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Investigators: Principal Investigator: Kenichi Hirano, MD, Ph.D, Department of Cardiovascular Medicine, Faculty of Internal Medicine, Graduate School of Osaka University, Japan; Principal Investigator: Elena M Pennisi, MD, Ph.D, Department of Neurology, San Filippo Neri Hospital, Rome, Italy

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2016
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: July 6, 2016
• First Submitted That Met QC Criteria: July 8, 2016
• First Posted (Estimate): July 13, 2016

Study Record Updates

• Last Update Posted (Actual): July 8, 2019
• Last Update Submitted That Met QC Criteria: July 4, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: neutral lipid storage disease; CNT-02; primary triglyceride deposit cardiomyovasculopathy (TGCV); neutral lipid storage disease with myopathy (NLSD-M)
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Congenital Abnormalities; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Neuromuscular Diseases; Skin Diseases, Genetic; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Skin Abnormalities; Keratosis; Ichthyosis; Muscular Diseases; Metabolic Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Ichthyosiform Erythroderma, Congenital
• Other Study ID Numbers: TRICVD1527; UMIN000023043 (Other Identifier: UMIN-CTR)