Effect of Glycerol Trierucate on Clinical Course of Adrenoleukodystrophy

• Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00004418
• Collaborator: (none)
• Enrollment: 126
• Locations: 2
• Arm: 1
• Duration (Months): 200
• Patients Per Site: 63
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

OBJECTIVES: I. Evaluate the clinical efficacy of combination glyceryl trierucate and glyceryl trioleate (Lorenzo's Oil) therapy in boys with X-linked adrenoleukodystrophy.

1. Compare the frequency and severity of neurological disability of study patients with untreated historical controls.

Condition or Disease	Intervention/Treatment	Phase
Adrenoleukodystrophy	Drug: glyceryl trierucate/glyceryl trioleate	Phase 2

Detailed Description

PROTOCOL OUTLINE: This is an open label study. Patients must follow dietary instructions as provided by the investigator. Patients receive 2-4 tablespoons of a mixture of glyceryl trierucate and glyceryl trioleate oil once daily. Patients complete a neuropsychological scoring scale questionnaire to measure neurological disability. Patients undergo physical examinations including magnetic resonance imaging and magnetic resonance spectroscopy of the head.

Patients are followed monthly for 6 months, then every 3 months until they reach the age of 13 years or death.

Study Design

• Study Type: Interventional
• Actual Enrollment: 126 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of Glyceryl Trierucate and Glyceryl Trioleate (Lorenzo's Oil) Therapy in Male Children With Adrenoleukodystrophy
• Study Start Date: Apr 1, 1998
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glyceryl trierucate/glyceryl trioleate Treatment of all enrolled participants. Dosage form is a liquid oil taken orally. Dose is to provide 20% of daily calories. Daily for duration of trial	Drug: glyceryl trierucate/glyceryl trioleate; Administration of glyceryl trierucate/glyceryl trioleate; Other Names: Lorenzo's oil

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Very Long Chain Fatty Acids (VLCFA) Blood Levels [Baseline, an average of 10 years, up to age 13]

   we will assess the change in very long-chain fatty acids as determined by reduction of blood level baseline C26:0 level.

Secondary Outcome Measures

1. Number of Participants With T2 MRI Abnormality [10 years]

   We used MRI to determine the number of participants with T2 MRI abnormality indicating childhood Adrenoleukodystrophy (ALD).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Months to 8 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion criteria.

1. Boys between the age of 18 months and 8 years of age

2. Biochemically proven asymptomatic X-linked adrenoleukodystrophy determined by elevation of very long chain fatty acids or DNA analysis.

3. Platelet count in normal range

Exclusion criteria.

1. Abnormal MRI consistent with childhood cerebral disease

2. Boys who have undergone bone marrow transplantation

3. Other medical condition which in the opinion of the investigator prevents evaluation or treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kennedy Krieger Institute	Baltimore	Maryland	United States	21205
2	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287-6681

Sponsors and Collaborators

• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Investigators

• Principal Investigator: Gerald V Raymond, M.D., Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
• ClinicalTrials.gov Identifier: NCT00004418
• Other Study ID Numbers: 199/13312; Nutricia-Loma Linda; KKI-FDR000685
• First Posted: Oct 19, 1999
• Last Update Posted: Oct 23, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.: adrenoleukodystrophy; inborn errors of metabolism; rare disease; sphingolipidoses
• Additional relevant MeSH terms: Adrenoleukodystrophy

Study Results

Participant Flow

Recruitment Details	An open trial of Lorenzo's oil spanning decades (1998-2013). Centered at the Kennedy Krieger.

Arm/Group Title	GTO/GTE Treatment
Arm/Group Description	Intervention: A mixture of glycerol trierucate (GTE) in glycerol trioleate (GTO) in combination with a diet low in saturated fats. GTO/GTE orally; 30-60 ml daily for study period glyceryl trierucate: Glyceryl trierucate is an oil to reduce very long chain fatty acids glyceryl trioleate: Patients receive 2-4 tablespoons of a mixture of glyceryl trierucate and glyceryl trioleate oil once daily.
Period Title: Overall Study
STARTED	126
COMPLETED	126
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	GTO/GTE Treatment
Arm/Group Description	Intervention: A mixture of glycerol trierucate (GTE) in glycerol trioleate (GTO) in combination with a diet low in saturated fats. GTO/GTE orally; 30-60 ml daily for study period glyceryl trierucate: Glyceryl trierucate is an oil to reduce very long chain fatty acids glyceryl trioleate: Patients receive 2-4 tablespoons of a mixture of glyceryl trierucate and glyceryl trioleate oil once daily.
Overall Participants	126
Age (Count of Participants)
<=18 years	126 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	3.25
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	126 100%
Region of Enrollment (participants) [Number]
United States	126 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Very Long Chain Fatty Acids (VLCFA) Blood Levels
Description	we will assess the change in very long-chain fatty acids as determined by reduction of blood level baseline C26:0 level.
Time Frame	Baseline, an average of 10 years, up to age 13

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GTO/GTE Treatment
Arm/Group Description	Intervention: A mixture of glycerol trierucate (GTE) in glycerol trioleate (GTO) in combination with a diet low in saturated fats. GTO/GTE orally; 30-60 ml daily for study period glyceryl trierucate: Glyceryl trierucate is an oil to reduce very long chain fatty acids glyceryl trioleate: Patients receive 2-4 tablespoons of a mixture of glyceryl trierucate and glyceryl trioleate oil once daily.
Measure Participants	126
Mean (Full Range) [mcg/mL]	0.41

2. Secondary Outcome

Title	Number of Participants With T2 MRI Abnormality
Description	We used MRI to determine the number of participants with T2 MRI abnormality indicating childhood Adrenoleukodystrophy (ALD).
Time Frame	10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GTO/GTE Treatment
Arm/Group Description	Intervention: A mixture of glycerol trierucate (GTE) in glycerol trioleate (GTO) in combination with a diet low in saturated fats. GTO/GTE orally; 30-60 ml daily for study period glyceryl trierucate: Glyceryl trierucate is an oil to reduce very long chain fatty acids glyceryl trioleate: Patients receive 2-4 tablespoons of a mixture of glyceryl trierucate and glyceryl trioleate oil once daily.
Measure Participants	126
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	10 years (throughout the study)
Arm/Group Title	GTO/GTE Treatment
Arm/Group Description	Intervention: A mixture of glycerol trierucate (GTE) in glycerol trioleate (GTO) in combination with a diet low in saturated fats. GTO/GTE orally; 30-60 ml daily for study period glyceryl trierucate: Glyceryl trierucate is an oil to reduce very long chain fatty acids glyceryl trioleate: Patients receive 2-4 tablespoons of a mixture of glyceryl trierucate and glyceryl trioleate oil once daily.
All Cause Mortality
	GTO/GTE Treatment
	Affected / at Risk (%)	# Events
Total	1/126 (0.8%)
Serious Adverse Events
	GTO/GTE Treatment
	Affected / at Risk (%)	# Events
Total	3/126 (2.4%)
Endocrine disorders
Death	1/126 (0.8%)	1
adrenal crisis	2/126 (1.6%)	2
Other (Not Including Serious) Adverse Events
	GTO/GTE Treatment
	Affected / at Risk (%)	# Events
Total	1/126 (0.8%)
Blood and lymphatic system disorders
Thrombocytopenia	1/126 (0.8%)	1
Hepatobiliary disorders
Elevation in liver function tests	0/126 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.