Glycerol trioctanoate

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Remarks:

Oral repeated dose

Type of information:

other: clinical case study in patients

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Retrospective case studies of the efficacy of caprylic triglyceride in mild-to-moderate Alzheimer’s disease

Author:

Maynard, S.D. and Gelblum, J.

Year:

2013

Bibliographic source:

Neuropsychiatr Dis Treat. 2013;9:1629-35.

Report date:

2013

Materials and methods

Type of study / information:

Caprylic triglyceride (CT) was administered in addition to other approved pharmacotherapy to eight patients with a diagnosis of probable Alzheimers's disease (AD) of mild-to-moderate severity.

Endpoint addressed:

other: monitoring of cognitive function using the Mini-Mental State Examination (MMSE)

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Case records from patients with Alzheimer Disease were reviewed. Eight patients aged 74-94 years had Mini-Mental State Examination (MMSE) evaluations before and after dosing with caprylic triglyceride at 20 g per day for 6-12 months.

GLP compliance:

no

Test material

Test material information

Details on test material:

Three caprylic fatty acids (C8:0) esterified to glycerol

Method

Ethical approval:

confirmed and informed consent free of coercion received

Remarks:

Patients or their caregivers provided informed written consent for extraction of all information presented in the publication from their medical records.

Details on study design:

6 male and 2 female patients aged 74-94 years, white or african-american, age at diagnosis 70-89 years.
Basis of diagnosis: cognitive testing; electroencephalogram; magnetic resonance imaging; signs and symptoms.
Patients were excluded if diagnosed with a comorbid disease known to adversely impact cognitive function.
None of the eight patients had evidence of pancreatic deficiency, diabetes, or alcohol abuse in their medical records.
All 8 patients had at least two Mini-Mental State Examination (MMSE) evaluations both before initiation of caprylic triglyceride and at least three measurements after initiation of this therapy.

Exposure assessment:

measured

Details on exposure:

20 g caprylic triglyceride per day was added to other therapy of the individual patients for a duration of at least 6 months up to 1 year.
Dose equivalent to 333 mg/kg bw/day for a body weight of 60 kg.

Results and discussion

Results:

Overall results for change in Mini-Mental State Examination scores: The mean (median) annual rates of decline prior to the initiation of caprylic triglyceride (CT) were −1.34 (−2.95) and those after addition of CT to ongoing pharmacotherapy were −0.64 (−0.55). Comparison of rates of decline before and after addition of CT to treatment indicated no significant difference for the two periods (P = 0.3735, Mann–Whitney U-test).
Results from this case review study indicated that addition of caprylic triglyceride to pharmacotherapy for Alzheimer's disease was associated with stable disease or improvement for some patients. In particular, addition of caprylic triglyderide seemed to have slowed the rate of decline, as measured by MMSE scores, compared with rates of decline reported in larger longitudinal studies.

Applicant's summary and conclusion

Conclusions:

In all eight cases of patients with Alzheimers's disease no adverse effects on the health status was seen upon administration of caprylic triglyceride (CAS 538-23-8) at 20 g/patient/day over at least 6 months. Moreover, administration of caprylic triglyderide seemed to have slowed the rate of mental decline, as measured by Mini Mental State Examination scores, compared with rates of decline reported in larger longitudinal studies. The administered dose is equivalent to 333 mg/kg bw/day for a body weight of 60 kg.