Study of Triheptanoin for Treatment of Long-Chain Fatty Acid Oxidation Disorder (Triheptanoin)

• ClinicalTrials.gov Identifier: NCT01379625
• Recruitment Status: Completed
• First Posted: June 23, 2011
• Results First Posted: March 23, 2017
• Last Update Posted: March 23, 2017
• Sponsor: Oregon Health and Science University
• Collaborator: University of Pittsburgh
• Information provided by (Responsible Party): Melanie B Gillingham, Oregon Health and Science University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Very Long-chain acylCoA Dehydrogenase (VLCAD) Deficiency; Carnitine Palmitoyltransferase 2 (CPT2) Deficiency; Mitochondrial Trifunctional Protein (TFP) Deficiency; Long-chain 3 hydroxyacylCoA Dehydrogenase (LCHAD) Deficiency
• Intervention: Drug: Triheptanoin
• Enrollment: 32

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Medium Chain Triglyceride (MCT)	Triheptanoin
Arm/Group Description	Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone	Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone
Period Title: Overall Study
Started	16	16
Completed	16	16
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Medium Chain Triglyceride (MCT)	Triheptanoin	Total
Arm/Group Description		Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone	Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone	Total of all reporting groups
Overall Number of Baseline Participants		16	16	32
Baseline Analysis Population Description		Subjects were 7 years of age or greater with one of 3 fatty acid oxidation disorders: CPT2, VLCAD or LCHAD/TFP.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	16 participants	16 participants	32 participants
		22.3 (12.7)	27.2 (15.9)	24.8 (14.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	16 participants	16 participants	32 participants
	Female	10 62.5%	10 62.5%	20 62.5%
	Male	6 37.5%	6 37.5%	12 37.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	16 participants	16 participants	32 participants
	Hispanic or Latino	1 6.3%	0 0.0%	1 3.1%
	Not Hispanic or Latino	15 93.8%	16 100.0%	31 96.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	16 participants	16 participants	32 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	16 100.0%	16 100.0%	32 100.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	16 participants	16 participants	32 participants
		16	16	32
Body Weight; Mean (Standard Deviation); Unit of measure: Kilograms
	Number Analyzed	16 participants	16 participants	32 participants
		67.1 (26.8)	62.1 (23.5)	64.6 (24.9)
Ejection Fraction [1] [2]; Mean (Standard Deviation); Unit of measure: Percent
	Number Analyzed	11 participants	10 participants	21 participants
		63 (5.3)	57 (9.2)	59.7 (8.0)
		[1] Measure Description: Echocardiogram ejection fraction as a %. This was not completed for all the participant. There were 11 participants in the MCT group and 10 participants in the Triheptanoin group who are included in this baseline measure.; [2] Measure Analysis Population Description: There was a change in the protocol from cardiac MRI to echo after the 1st 7 participants and some of the echocardiogram results were unreadable due to technical errors. A total of 11 subjects in the MCT and 10 subjects in triheptanoin group were analyzed.
Exercise Heart Rate [1]; Mean (Standard Deviation); Unit of measure: Beats per minute
	Number Analyzed	16 participants	16 participants	32 participants
		132 (7)	125 (12)	128 (10)
		[1] Measure Description: All participants performed a moderate intensity exercise treadmill walking at an estimated 60% of their estimated max heart rate for 40 minutes. The exercise heart rate at minute 30 when the exercise was steady is reported.
Total Energy Expenditure [1] [2]; Mean (Standard Deviation); Unit of measure: Kcal/day
	Number Analyzed	15 participants	15 participants	30 participants
		2567 (604)	2230 (512)	2392 (572)
		[1] Measure Description: Total energy expenditure in kcal/day was measured by doubly labled water in 12 subjects in the MCT group and in 13 of the subjects in the Triheptanoin group.; [2] Measure Analysis Population Description: One participant in the MCT group and one participant in the Triheptanoin group did not return their urine samples for the doubly labeled water analysis. A total of 15 in each group were analyzed.

Outcome Measures

1. Primary Outcome

Title	Energy Expenditure
Description	Total energy expenditure will be measured by doubly labeled water and resting energy expenditure will be measured by indirect calorimetry at baseline and again after 4 months of either MCT or trihpetanoin treatment.
Time Frame	change from baseline after 4 months of treatment

Outcome Measure Data

Analysis Population Description

One subject in each group did not complete the doubly labeled water measures. A total of 15 in each group measured total energy expenditure at baseline and at the end of the study. This value compares the change over treatment.

Arm/Group Title	Medium Chain Triglyceride (MCT)	Triheptanoin
Arm/Group Description:	Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone	Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone
Overall Number of Participants Analyzed	15	15
Mean (Standard Deviation); Unit of Measure: kcal/day
	-73 (335)	107 (387)

2. Primary Outcome

Title	Ejection Fraction
Description	Change in resting ejection fraction over 4 month treatment period
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

Change in resting ejection fraction over 4 month treatment period calculated as: 4 month ejection fraction-baseline ejection fraction. Only participants with available data are included in this analysis.

Arm/Group Title	Medium Chain Triglyceride (MCT)	Triheptanoin
Arm/Group Description:	Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone	Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone
Overall Number of Participants Analyzed	11	10
Mean (Standard Deviation); Unit of Measure: percent
	-1.91 (4.16)	2.14 (4.43)

3. Secondary Outcome

Title	Exercise Heart Rate
Description	Subjects will complete a submaximal treadmill exercise study at baseline. Exercise heart heart, ventilation and perceived exertion will be measured. Subjects will be randomized to MCT or triheptanoin supplementation for 4 months. At the end of treatment, the exercise test will be repeated keeping work performed constant. Change in exercise heart rate, ventilation and exertion will be compared between groups.
Time Frame	change from baseline to 4 months of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Medium Chain Triglyceride (MCT)	Triheptanoin
Arm/Group Description:	Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone	Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone
Overall Number of Participants Analyzed	16	16
Mean (Standard Deviation); Unit of Measure: beats per minute
	-0.1 (9.6)	-12.6 (34)

Adverse Events

Time Frame	Four months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Medium Chain Triglyceride (MCT)		Triheptanoin
Arm/Group Description	Subjects randomized to consume 20% of energy from MCT Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone		Subject randomized to consume 20% of energy from triheptanoin. Triheptanoin: Triglyceride with three heptanoin or 7 carbon fatty acids esterified to a glycerol backbone
All-Cause Mortality
	Medium Chain Triglyceride (MCT)		Triheptanoin
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Medium Chain Triglyceride (MCT)		Triheptanoin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0.00%)		0/16 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Medium Chain Triglyceride (MCT)		Triheptanoin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/16 (75.00%)		11/16 (68.75%)
Gastrointestinal disorders
Gastrointestinal Upset † 1 [1]	12/16 (75.00%)	38	11/16 (68.75%)	24
Diarrhea/Loose stools † 1 [2]	6/16 (37.50%)	12	5/16 (31.25%)	9
Musculoskeletal and connective tissue disorders
Rhabdomyolysis † 1 [3]	4/16 (25.00%)	7	5/16 (31.25%)	7
muscle pain/ elevated CPK † 1 [4]	10/16 (62.50%)	18	11/16 (68.75%)	16
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, 21 CRF 312; [1] Gastrointestinal Upset including stomach pain, burning, or cramping.; [2] Report of diarrhea or loose stools during the treatment period.; [3] Acute rhabdomyolysis requiring hospitalization is expected. This is a known complication of fatty acid oxidation disorders.; [4] This is an anticipated adverse event because muscle pain with elevated CPK is a complication of a fatty acid oxidation disorder.

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

• Name/Title: Dr. Melanie Gillingham
• Organization: Oregon Health & Science University
• Phone: 503-494-1682
• EMail: gillingm@ohsu.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gillingham MB, Heitner SB, Martin J, Rose S, Goldstein A, El-Gharbawy AH, Deward S, Lasarev MR, Pollaro J, DeLany JP, Burchill LJ, Goodpaster B, Shoemaker J, Matern D, Harding CO, Vockley J. Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: a double blinded, randomized controlled trial. J Inherit Metab Dis. 2017 Nov;40(6):831-843. doi: 10.1007/s10545-017-0085-8. Epub 2017 Sep 4.

• Responsible Party: Melanie B Gillingham, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT01379625
• Other Study ID Numbers: FD003895
• First Submitted: June 21, 2011
• First Posted: June 23, 2011
• Results First Submitted: July 12, 2016
• Results First Posted: March 23, 2017
• Last Update Posted: March 23, 2017