Oral Ketones and Exercise Among Patients With Long-chain Fatty Acid Oxidation Disorders

Safety and Tolerability of Oral Ketones and Exercise Among Patients With Long-chain Fatty Acid Oxidation Disorders

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.

Study Overview

• Status: Completed
• Conditions: Trifunctional Protein Deficiency; Very Long Chain Acyl Coa Dehydrogenase Deficiency; Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency; Carnitine Palmitoyltransferase Deficiency 2
• Intervention / Treatment: Dietary supplement: Nutritional Ketone Supplement; Dietary supplement: Isocaloric Placebo Supplement

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nutrition Ketogenic Supplement; The Ketone pre-exercise beverage is a nutritional supplement. The supplement will be provided by Nestle as powered sachets to mix in water. It contains a mix of D-beta-hydroxybutyrate salts, flavors and stevia.	Dietary supplement: Nutritional Ketone Supplement; Mix of sodium, calcium, and magnesium salts of D-beta-hydroxybutyrate with nicotinamide riboside chloride, flavors and stevia sweetener; Other Names: NKS
Sham Comparator: Isocaloric Placebo Supplement; The maltodextrin pre-exercise beverage is a nutritional supplement. The supplement will be provided by Nestle as powered sachets to mix in water. It contains an isocaloric amount of maltodextrin, flavors and stevia similar to the ketone beverage.	Dietary supplement: Isocaloric Placebo Supplement; Maltodextrin with flavors and stevia sweetener

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events- incidence	Number of Adverse events	2 hours after product intake
Adverse Events- type	Description of Adverse events: categorical	2 hours after product intake
Adverse Events- severity	Severity of adverse event: grade 1-5	2 hours after product intake
Adverse Events- causal relationship	Yes/No related to product intake	2 hours after product intake
Abdominal discomfort	visual analogue scale (VAS) 0-10	2 hours after product intake
Decreased appetite	visual analogue scale (VAS) 0-10	2 hours after product intake
Gastric reflux	visual analogue scale (VAS) 0-10	2 hours after product intake
Nausea	visual analogue scale (VAS) 0-10	2 hours after product intake
Diarrhea	visual analogue scale (VAS) 0-10	2 hours after product intake
Headache	visual analogue scale (VAS) 0-10	2 hours after product intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Ketones	plasma beta-hydroxybutyrate concentration	20 minutes after moderate intensity exercise
Blood Creatine Kinase	plasma CK concentration	20 minutes after moderate intensity exercise
Blood Glucose	serum glucose	20 minutes after moderate intensity exercise
Blood Lactate	serum lactate concentration	20 minutes after moderate intensity exercise
Blood Pressure	diastolic BP	peak 40 minute exercise
Blood Pressure	systolic BP	peak 40 minute exercise
Perceived exertion	Borg scale 1-20	peak 40 minute exercise
Respiratory Exchange Ratio	VCO2/VO2 0.7 - 1.0	peak 40 minute exercise
Heart Rate	beats per minute	peak 40 minute exercise

Collaborators and Investigators

• Sponsor: Oregon Health and Science University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): January 22, 2024

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Deficiency Diseases; Malnutrition; Protein Deficiency
• Other Study ID Numbers: 23859

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Participants will be provided with creatine kinase lab test and body composition measurement. The results of their creatine kinase lab test will be placed in their medical record. Results of the study will be written in a published manuscript and summarized in a cover letter to be sent via mail or email to the participant after publication of the data.
• IPD Sharing Time Frame: The published manuscript will be available approximately 6-9 months after the conclusion of the study.
• IPD Sharing Access Criteria: not applicable. A reprint will be sent to participants.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No