Carnitine Palmitoyltransferase Deficiency 2, Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency, Trifunctional Protein Deficiency, Very Long Chain Acyl Coa Dehydrogenase Deficiency
Conditions
Brief summary
The purpose of the study is to determine if an oral ketone beverage is safe and well-tolerated during moderate intensity exercise in participants with long-chain fatty acid oxidation disorders and if it will raise blood ketones to levels similar to that reported among normal healthy subjects.
Detailed description
Purpose: Subjects with long-chain fatty acid oxidation disorders (LC-FAOD) do not make ketones during fasting or with exercise. Ketones are an important alternative energy substrate during moderate exercise, sparing the oxidation of glucose and providing a source of ATP to the central nervous system and exercising muscle. Fatty acid oxidation in the liver is required to make ketones. Subjects with a LC-FAOD cannot generate ketones because of their block in fatty acid oxidation during exercise. Providing ketones in an oral ketone beverage may increase blood ketones with exercise to levels normally observed in humans. Aim: To determine the safety and tolerability of an oral ketone beverage during moderate intensity exercise among subjects with a LC-FAOD compared to an isocaloric maltodextrin beverage, and to determine blood ketone concentrations. Hypothesis: Oral consumption of a ketone beverage before moderate intensity exercise will be safe and well-tolerated, and will raise blood ketones among subjects with a LC-FAOD to concentrations similar to that reported in the literature among normal healthy subjects.
Interventions
DIETARY_SUPPLEMENTNutritional Ketone Supplement
Mix of sodium, calcium, and magnesium salts of D-beta-hydroxybutyrate with nicotinamide riboside chloride, flavors and stevia sweetener
DIETARY_SUPPLEMENTIsocaloric Placebo Supplement
Maltodextrin with flavors and stevia sweetener
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Sachets of the ketone or maltodextrin powder are coded and packaged identically. The bionutrition unit will prepare the beverage and maintain the randomization code and the code for the ketone and maltodextrin products.
Intervention model description
Subjects with either CPT2, TFP, LCHAD or VLCAD deficiency will be randomized to receive a ketone beverage (see composition in Appendix A) or an isocaloric maltodextrin control beverage (see composition in Appendix A) before moderate intensity exercise. Twenty minutes after consuming the pre-exercise beverage, subjects will complete a moderate intensity treadmill exercise test for 45 minutes. After a washout period of 48 hours, subjects will repeat the exercise. During the 2nd exercise test subjects will crossover to the beverage not consumed during the 1st exercise study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* confirmed diagnosis of VLCAD, LCHAD/TFP or CPT2 deficiency * speak English * willing to complete 2 moderate intensity exercise treadmills
Exclusion criteria
* subjects actively participating in another research study that prohibits their participation * pregnant females * subjects with diabetes or taking medications to treat diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Headache | 2 hours after product intake | visual analogue scale (VAS) 0-10 |
| Adverse Events- type | 2 hours after product intake | Description of Adverse events: categorical |
| Adverse Events- severity | 2 hours after product intake | Severity of adverse event: grade 1-5 |
| Adverse Events- causal relationship | 2 hours after product intake | Yes/No related to product intake |
| Abdominal discomfort | 2 hours after product intake | visual analogue scale (VAS) 0-10 |
| Decreased appetite | 2 hours after product intake | visual analogue scale (VAS) 0-10 |
| Gastric reflux | 2 hours after product intake | visual analogue scale (VAS) 0-10 |
| Nausea | 2 hours after product intake | visual analogue scale (VAS) 0-10 |
| Diarrhea | 2 hours after product intake | visual analogue scale (VAS) 0-10 |
| Adverse Events- incidence | 2 hours after product intake | Number of Adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Creatine Kinase | 20 minutes after moderate intensity exercise | plasma CK concentration |
| Blood Glucose | 20 minutes after moderate intensity exercise | serum glucose |
| Blood Lactate | 20 minutes after moderate intensity exercise | serum lactate concentration |
| Blood Pressure | peak 40 minute exercise | diastolic BP |
| Perceived exertion | peak 40 minute exercise | Borg scale 1-20 |
| Respiratory Exchange Ratio | peak 40 minute exercise | VCO2/VO2 0.7 - 1.0 |
| Heart Rate | peak 40 minute exercise | beats per minute |
| Blood Ketones | 20 minutes after moderate intensity exercise | plasma beta-hydroxybutyrate concentration |
Countries
United States
Outcome results
None listed