Myalgic EncephalomyelitisNCT05273372
RESTORE ME -- RCT of Oxaloacetate on Improving Fatigue in ME/CFS
A study testing Medical Food - Anhydrous Enol-Oxaloacetate in people with Myalgic Encephalomyelitis and Chronic Fatigue Syndrome, run by Terra Biological LLC at 1 site in United States.
Trial summary
There is no approved treatment for fatigue in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a condition with as many as 2.5 million people in the US. Initial case studies have shown an improvement in fatigue in ME/CFS with anhydrous enol-oxaloacetate (AEO). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, Fatigue
- What is being tested?
- Medical Food - Anhydrous Enol-Oxaloacetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Mar 2022to 15 Nov 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who meet all of the following criteria are eligible to participate in the study:
- Provision of signed and dated informed consent form
- Ability to read, understand or speak English
- Diagnosed with ME/CFS and meet the IOM Diagnostic Criteria for ME/CFS (2015)
- Relatively stable state of illness for the past 3 months that is characterized by >2 and <6 hours of daily upright activity
- Male or female, between the ages of 18 and 65 years old
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- No evidence of active infection with SARS-CoV-2 documented by a negative test at Visit 1
- Agree to refrain from taking medications that would affect assessment of the effectiveness of study dietary supplement for the duration of the study
- Females of childbearing potential should be on adequate contraception such as oral, implantable, injectable or transdermal hormonal contraceptives (should have been used for a minimum of one full cycle prior to administration of study drug), intrauterine devices (IUD), vasectomized partner, double barrier method (male or female condom, sponge, diaphragm or vaginal ring with simultaneous use of spermicidal jelly or cream)
- Each patient of child-bearing potential must have a negative urine pregnancy test at Visit 1. The urine test at Visit 1 must both be confirmed negative prior to randomization. Women of child-bearing potential will have a urine pregnancy test at each visit (2-4) and it must be negative to continue. Women who are confirmed to be of non-childbearing potential do not require pregnancy testing. To be considered of non-child-bearing potential, the patient must be: post-menopausal (defined as no menses for at least one year); or surgically sterile (s/p hysterectomy, bilateral oophorectomy or bilateral tubal ligation at least 6 months prior to randomization); or at least 3 months s/p a non-surgical permanent sterilization procedure
- History of fatigue and post-exertional malaise (PEM)
- Stated willingness to comply with all study procedures and remain available for the study duration
- Have mobile (smart) phone and access to the internet
- Willingness to wear a device on their ankle
Who cannot join
- A patient who meets any of the following criteria will be excluded from participation in this study:
- A positive rapid COVID-19 antigen test at Visit 1
- Alternate medical or psychiatric illness that could explain the ME/CFS symptoms
- Severe ME/CFS with less than 2 hours of upright activity a day
- Active or uncontrolled co-morbidities which in the opinion of the PI may interfere with the ability of the patient to participate in the study. Co-morbidities may include acute infection, Crohn's disease, diabetes mellitus (Type 1 or Type 2, evidenced by a history of HbA1c > 7 at any time), Guillain-Barre syndrome, lupus, multiple sclerosis, myasthenia gravis, rheumatoid arthritis, or other such diseases that may be exclusionary. Particularly conditions or medications that cause immunodeficiency or immunosuppression will be excluded. Examples of such conditions can be found in the tables "Causes of Secondary Immunodeficiency" and "Some Drugs that Cause Immunosuppression" in the "Merck Manual"
- Body Mass Index > 35
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- Participating in another clinical treatment trial, or symptoms improving as a result of treatment intervention in the past 3 months
- Current treatment with stimulants including methylphenidate, amphetamine-dextroamphetamine, lisdexamfetamine, modafinil, armodafinil
- Pregnancy, or while breast feeding. Women should not be enrolled within 6 months of giving birth and within 3 months of cessation of breast feeding.
- History of:
- Major depression with psychotic or melancholic features before the diagnosis of ME/CFS, or active depression (major depression with psychotic or melancholic features) as determined by self-report
- Untreated endocrine diagnoses including hypothyroidism (Hashimoto's, etc.), Grave's disease, adrenal insufficiency, hypogonadism (testosterone deficiency), diabetes mellitus or insipidus
- Significant head injury in the last 3 years, concussion with loss of consciousness, brain surgery, an automobile accident with head/neck injury, and/or other traumatic brain injury
- A supra-ventricular tachycardia or ventricular tachycardia, e.g., atrial fibrillation or flutter, paroxysmal atrial fibrillation, junctional tachycardia, ventricular tachycardia
- Symptomatic hypotension defined as rested sitting systolic BP < 100 mmHg or rested sitting diastolic BP < 60 mmHg
- Substance abuse in the past 12 months as determined by self-report • Improvement in overall ME/CFS symptoms as a result of any treatment intervention in the past 3 months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Double Blind Placebo Controlled Trial to Determine the Effects of Oxaloacetate on Improving Fatigue in ME/CFS
There is no approved treatment for fatigue in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a condition with as many as 2.5 million people in the US. Initial case studies have shown an improvement in fatigue in ME/CFS with anhydrous enol-oxaloacetate (AEO).
This randomized, double blinded, placebo controlled trial will seek to further evaluate the efficacy of AEO to reduce fatigue in ME/CFS, based on change in the Chalder Fatigue Score (Likert Scoring) of the AEO group against the placebo group at 90 days.
Read more
As secondary evaluations on other core ME/CFS symptoms, the investigators are measuring the health related quality of life as assessed by the SF-36, hours of upright activity, functional capacity (activity, steps, cognition, and heart rate variability), and general health status (global change, vitals)
Finally, this test will gain preliminary insights on the safety, tolerability, and efficacy of AEO in ME/CFS patients.
Read the detailed description
Anhydrous Enol-Oxaloacetate is a patented thermally stabilized oxaloacetate compound with a multiple year stability rating that when ingested forms bioidentical oxaloacetate. Oxaloacetate is a human metabolite involved in many biochemical reactions in the cytosol and mitochondrial, and is key to energy production.
The investigators will conduct a randomized double blind placebo control trial to determine the effects of AEO on improving fatigue in ME/CFS. The primary measurement with be the Chalder Fatigue Score. The trial will be performed at one site, the Bateman Horne Center, which specializes in the treatment of ME/CFS. The trial will also evaluate the effect of AEO on other core ME/CFS symptoms, health related quality of life as assessed by the SF-36, hours of upright activity, functional capacity (upright activity, steps, cognition, and heart rate variability) and general health status (global change, vitals). The trial will also gain preliminary insights on the safety, tolerability, and efficacy of AEO in ME/CFS patients.
Treatment in the trial will be over a 90-day period for each patient. Participants will be primarily recruited from Bateman Horne's current patients and BHCs databases of research participants. Participants will be screened by telephone for potential eligibility, and if eligible, will be invited to an in person visit at Bateman Horne Center to further confirm eligibility and obtain informed consent. Evaluation will include assessment of vital signs, weight, determination of 5-minute a standard 12-lead electrocardiogram to determine heart rate variability (HRV), cognitive testing, and collection of a fasting blood. Women who could potentially be pregnant will undergo pregnancy testing. Participants will complete baseline questionnaires that assess ME/CFS symptoms, and will undergo cognitive testing, along with a blood draw for biobanking for future banking and eventual metabolomic testing that could include assays such as metabolomics, lipidomics and transcriptomics. Subjects will be provided with a device to wear on their ankle that will determine daily steps and upright activity.
On Visit 1 participants will receive two bottles of 90-day supply of the study capsules treatment and will be instructed to take two 500 mg capsule at breakfast and again at lunch. When participants return for Visit 2, they will bring the bottles of study product with them. BHC will take account of the initial 4-week supplies of the product remaining and provide the participant with another bottle of product. When participants return for study dietary supplement will be distributed at Visit 2 and Visit 3, they will bring the bottles of study project with them, BHC will take account of the remaining product and provide the participant with another bottle. For the final Visit 4, participant will bring the bottles of study product with them and BHC will take account of remaining study product.
Participants will be contacted once every two weeks by the study coordinator to assess for any side effects or difficulty taking the study dietary supplement. They will be asked to return for an in person visit every 4 weeks for 90 days at which time any symptoms or toxicities will be formally documented, and they will complete follow-up questionnaires to assess symptoms, cognition, and heart rate variability. After 12 weeks there will be a final in person visit with a final physical examination, 5-minute HRVEKG, cognitive testing, and symptom assessment.
- Conditions
- Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, Fatigue
- Being tested
- Placebo, Medical Food - Anhydrous Enol-Oxaloacetate
- Medical subject headings
- Fatigue Syndrome, Chronic, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Also called White Rice Flour
Placebo treatment with the food white rice flour. 1,000 mg BID
Medical Food - Anhydrous Enol-OxaloacetateOther
Also called Oxaloacetate
Active treatment with oxaloacetate. 1,000 mg BID
| Study group | Role | What they receive |
|---|---|---|
| Oxaloacetate | Experimental | 500 mg anhydrous enol-oxaloacetate in hypromellose capsules (veggie caps). 2 capsules with breakfast and 2 capsules with lunch (1,000 mg BID) for 90 days. Receives: Other: Medical Food - Anhydrous Enol-Oxaloacetate |
| Placebo | Placebo comparator | 500 mg white rice flour in hypromellose capsules (veggie caps). 2 capsules with breakfast and 2 capsules with lunch (1,000 mg BID) for 90 days. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of Fatigue
Reduction in fatigue, Likert Scoring, on the Chalder Fatigue Scale 0-33 Point Scale, with 0 being no fatigue, and 33 being maximum measurable fatigue
Measured: 90 days
Secondary outcomes (3)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Comparison of adverse events in the treatment group as opposed to the placebo group
Measured: 90 days
Physical Functioning on the SF-36
Evaluation of the SF-36 for physical functioning, role physical, bodily pain, and others
Measured: 90 days
Patient Global Impression of Change Questionnaire, 7 point scale, -3 to +3, with the higher score indicating more improvement
Measurement of patlient's rating of overall improvement
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2022
- Study start15 Mar 2022
- Primary completion15 Jun 2024
- Study completion15 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Myalgic EncephalomyelitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Placebo-controlled double blinded 2 arm study. 40 patients in treatment arm, 40 patients in placebo arm.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Terra Biological LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bateman Horne Center
- Responsible party
- Sponsor
- Investigators
- Suzanne D Vernon, Ph.D., Principal investigator, Bateman Horne Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05273372
- Sponsor's protocol ID
- TB-2022-AEO ME/CFS v1.6
- Status last verified
- Nov 2024
- First submitted
- 18 Feb 2022
- Last updated
- 4 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: At this time the IPD is not available to other researchers.
Publications
Germain A, Ruppert D, Levine SM, Hanson MR. Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol Biosyst. 2017 Jan 31;13(2):371-379. doi: 10.1039/c6mb00600k.
PubMed 28059425Germain A, Barupal DK, Levine SM, Hanson MR. Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids. Metabolites. 2020 Jan 14;10(1):34. doi: 10.3390/metabo10010034.
PubMed 31947545Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015 Feb 10. Available from http://www.ncbi.nlm.nih.gov/books/NBK274235/
PubMed 25695122Keller BA, Pryor JL, Giloteaux L. Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO(2)peak indicates functional impairment. J Transl Med. 2014 Apr 23;12:104. doi: 10.1186/1479-5876-12-104.
PubMed 24755065Mandarano AH, Maya J, Giloteaux L, Peterson DL, Maynard M, Gottschalk CG, Hanson MR. Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations. J Clin Invest. 2020 Mar 2;130(3):1491-1505. doi: 10.1172/JCI132185.
PubMed 31830003McHorney CA, Ware JE Jr, Lu JF, Sherbourne CD. The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups. Med Care. 1994 Jan;32(1):40-66. doi: 10.1097/00005650-199401000-00004.
PubMed 8277801Nagy-Szakal D, Barupal DK, Lee B, Che X, Williams BL, Kahn EJR, Ukaigwe JE, Bateman L, Klimas NG, Komaroff AL, Levine S, Montoya JG, Peterson DL, Levin B, Hornig M, Fiehn O, Lipkin WI. Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics. Sci Rep. 2018 Jul 3;8(1):10056. doi: 10.1038/s41598-018-28477-9.
PubMed 29968805Nkiliza A, Parks M, Cseresznye A, Oberlin S, Evans JE, Darcey T, Aenlle K, Niedospial D, Mullan M, Crawford F, Klimas N, Abdullah L. Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms. J Transl Med. 2021 Aug 28;19(1):370. doi: 10.1186/s12967-021-03035-6.
PubMed 34454515Ruban A, Berkutzki T, Cooper I, Mohar B, Teichberg VI. Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas. Invest New Drugs. 2012 Dec;30(6):2226-35. doi: 10.1007/s10637-012-9799-5.
PubMed 22392507Swerdlow RH, Bothwell R, Hutfles L, Burns JM, Reed GA. Tolerability and pharmacokinetics of oxaloacetate 100 mg capsules in Alzheimer's subjects. BBA Clin. 2016 Mar 10;5:120-3. doi: 10.1016/j.bbacli.2016.03.005. eCollection 2016 Jun.
PubMed 27051598Tully L, Humiston J, Cash A. Oxaloacetate reduces emotional symptoms in premenstrual syndrome (PMS): results of a placebo-controlled, cross-over clinical trial. Obstet Gynecol Sci. 2020 Mar;63(2):195-204. doi: 10.5468/ogs.2020.63.2.195. Epub 2020 Feb 25.
PubMed 32206660Vernon SD, Whistler T, Cameron B, Hickie IB, Reeves WC, Lloyd A. Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus. BMC Infect Dis. 2006 Jan 31;6:15. doi: 10.1186/1471-2334-6-15.
PubMed 16448567Vidoni ED, Choi IY, Lee P, Reed G, Zhang N, Pleen J, Mahnken JD, Clutton J, Becker A, Sherry E, Bothwell R, Anderson H, Harris RA, Brooks W, Wilkins HM, Mosconi L, Burns JM, Swerdlow RH. Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients. Alzheimers Dement. 2021 Jan;17(1):7-17. doi: 10.1002/alz.12156. Epub 2020 Jul 27.
PubMed 32715609Whistler T, Taylor R, Craddock RC, Broderick G, Klimas N, Unger ER. Gene expression correlates of unexplained fatigue. Pharmacogenomics. 2006 Apr;7(3):395-405. doi: 10.2217/14622416.7.3.395.
PubMed 16610950Wilkins HM, Harris JL, Carl SM, E L, Lu J, Eva Selfridge J, Roy N, Hutfles L, Koppel S, Morris J, Burns JM, Michaelis ML, Michaelis EK, Brooks WM, Swerdlow RH. Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis. Hum Mol Genet. 2014 Dec 15;23(24):6528-41. doi: 10.1093/hmg/ddu371. Epub 2014 Jul 15.
PubMed 25027327
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double Blind Placebo Controlled Trial to Determine the Effects of Oxaloacetate on Improving Fatigue in ME/CFS
- ClinicalTrials.gov ID
- NCT05273372
- Acronym / sponsor ID
- TB-2022-AEO ME/CFS v1.6
- Conditions
- Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, Fatigue
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Terra Biological LLCIndustry (pharma, biotech, devices)
- Collaborators
- Bateman Horne Center
- Study start
- 15 Mar 2022 (actual)
- Primary completion
- 15 Jun 2024 (actual)
- Study completion
- 15 Nov 2024 (actual)
- First posted
- 10 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There is no approved treatment for fatigue in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a condition with as many as 2.5 million people in the US. Initial case studies have shown an improvement in fatigue in ME/CFS with anhydrous enol-oxaloacetate (AEO).
This randomized, double blinded, placebo controlled trial will seek to further evaluate the efficacy of AEO to reduce fatigue in ME/CFS, based on change in the Chalder Fatigue Score (Likert Scoring) of the AEO group against the placebo group at 90 days.
As secondary evaluations on other core ME/CFS symptoms, the investigators are measuring the health related quality of life as assessed by the SF-36, hours of upright activity, functional capacity (activity, steps, cognition, and heart rate variability), and general health status (global change, vitals)
Finally, this test will gain preliminary insights on the safety, tolerability, and efficacy of AEO in ME/CFS patients.
Detailed description
Anhydrous Enol-Oxaloacetate is a patented thermally stabilized oxaloacetate compound with a multiple year stability rating that when ingested forms bioidentical oxaloacetate. Oxaloacetate is a human metabolite involved in many biochemical reactions in the cytosol and mitochondrial, and is key to energy production.
The investigators will conduct a randomized double blind placebo control trial to determine the effects of AEO on improving fatigue in ME/CFS. The primary measurement with be the Chalder Fatigue Score. The trial will be performed at one site, the Bateman Horne Center, which specializes in the treatment of ME/CFS. The trial will also evaluate the effect of AEO on other core ME/CFS symptoms, health related quality of life as assessed by the SF-36, hours of upright activity, functional capacity (upright activity, steps, cognition, and heart rate variability) and general health status (global change, vitals). The trial will also gain preliminary insights on the safety, tolerability, and efficacy of AEO in ME/CFS patients.
Treatment in the trial will be over a 90-day period for each patient. Participants will be primarily recruited from Bateman Horne's current patients and BHCs databases of research participants. Participants will be screened by telephone for potential eligibility, and if eligible, will be invited to an in person visit at Bateman Horne Center to further confirm eligibility and obtain informed consent. Evaluation will include assessment of vital signs, weight, determination of 5-minute a standard 12-lead electrocardiogram to determine heart rate variability (HRV), cognitive testing, and collection of a fasting blood. Women who could potentially be pregnant will undergo pregnancy testing. Participants will complete baseline questionnaires that assess ME/CFS symptoms, and will undergo cognitive testing, along with a blood draw for biobanking for future banking and eventual metabolomic testing that could include assays such as metabolomics, lipidomics and transcriptomics. Subjects will be provided with a device to wear on their ankle that will determine daily steps and upright activity.
On Visit 1 participants will receive two bottles of 90-day supply of the study capsules treatment and will be instructed to take two 500 mg capsule at breakfast and again at lunch. When participants return for Visit 2, they will bring the bottles of study product with them. BHC will take account of the initial 4-week supplies of the product remaining and provide the participant with another bottle of product. When participants return for study dietary supplement will be distributed at Visit 2 and Visit 3, they will bring the bottles of study project with them, BHC will take account of the remaining product and provide the participant with another bottle. For the final Visit 4, participant will bring the bottles of study product with them and BHC will take account of remaining study product.
Participants will be contacted once every two weeks by the study coordinator to assess for any side effects or difficulty taking the study dietary supplement. They will be asked to return for an in person visit every 4 weeks for 90 days at which time any symptoms or toxicities will be formally documented, and they will complete follow-up questionnaires to assess symptoms, cognition, and heart rate variability. After 12 weeks there will be a final in person visit with a final physical examination, 5-minute HRVEKG, cognitive testing, and symptom assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Placebo-controlled double blinded 2 arm study. 40 patients in treatment arm, 40 patients in placebo arm.
| Arm | Type | Receives |
|---|---|---|
| Oxaloacetate | Experimental | Other: Medical Food - Anhydrous Enol-Oxaloacetate500 mg anhydrous enol-oxaloacetate in hypromellose capsules (veggie caps). 2 capsules with breakfast and 2 capsules with lunch (1,000 mg BID) for 90 days. |
| Placebo | Placebo comparator | Other: Placebo500 mg white rice flour in hypromellose capsules (veggie caps). 2 capsules with breakfast and 2 capsules with lunch (1,000 mg BID) for 90 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients who meet all of the following criteria are eligible to participate in the study:
Key exclusion criteria (16 listed)
- A patient who meets any of the following criteria will be excluded from participation in this study:
- Major depression with psychotic or melancholic features before the diagnosis of ME/CFS, or active depression (major depression with psychotic or melancholic features) as determined by self-report
- Untreated endocrine diagnoses including hypothyroidism (Hashimoto's, etc.), Grave's disease, adrenal insufficiency, hypogonadism (testosterone deficiency), diabetes mellitus or insipidus
- Significant head injury in the last 3 years, concussion with loss of consciousness, brain surgery, an automobile accident with head/neck injury, and/or other traumatic brain injury
- A supra-ventricular tachycardia or ventricular tachycardia, e.g., atrial fibrillation or flutter, paroxysmal atrial fibrillation, junctional tachycardia, ventricular tachycardia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboAlso: White Rice FlourPlacebo treatment with the food white rice flour. 1,000 mg BID | Other | Placebo |
| Medical Food - Anhydrous Enol-OxaloacetateAlso: OxaloacetateActive treatment with oxaloacetate. 1,000 mg BID | Other | Oxaloacetate |
Primary outcome
Reduction of Fatigue
Time frame: 90 days
Reduction in fatigue, Likert Scoring, on the Chalder Fatigue Scale 0-33 Point Scale, with 0 being no fatigue, and 33 being maximum measurable fatigue
3 secondary outcomes
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 90 days
Physical Functioning on the SF-36
Time frame: 90 days
Patient Global Impression of Change Questionnaire, 7 point scale, -3 to +3, with the higher score indicating more improvement
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Background: PubMed 28059425Germain A, Ruppert D, Levine SM, Hanson MR. Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol Biosyst. 2017 Jan 31;13(2):371-379. doi: 10.1039/c6mb00600k.
- Background: PubMed 31947545Germain A, Barupal DK, Levine SM, Hanson MR. Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids. Metabolites. 2020 Jan 14;10(1):34. doi: 10.3390/metabo10010034.
- Background: PubMed 25695122Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; Board on the Health of Select Populations; Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015 Feb 10. Available from http://www.ncbi.nlm.nih.gov/books/NBK274235/
- Background: PubMed 24755065Keller BA, Pryor JL, Giloteaux L. Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO(2)peak indicates functional impairment. J Transl Med. 2014 Apr 23;12:104. doi: 10.1186/1479-5876-12-104.
- Background: PubMed 31830003Mandarano AH, Maya J, Giloteaux L, Peterson DL, Maynard M, Gottschalk CG, Hanson MR. Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations. J Clin Invest. 2020 Mar 2;130(3):1491-1505. doi: 10.1172/JCI132185.
- Background: PubMed 8277801McHorney CA, Ware JE Jr, Lu JF, Sherbourne CD. The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups. Med Care. 1994 Jan;32(1):40-66. doi: 10.1097/00005650-199401000-00004.
- Background: PubMed 29968805Nagy-Szakal D, Barupal DK, Lee B, Che X, Williams BL, Kahn EJR, Ukaigwe JE, Bateman L, Klimas NG, Komaroff AL, Levine S, Montoya JG, Peterson DL, Levin B, Hornig M, Fiehn O, Lipkin WI. Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics. Sci Rep. 2018 Jul 3;8(1):10056. doi: 10.1038/s41598-018-28477-9.
- Background: PubMed 34454515Nkiliza A, Parks M, Cseresznye A, Oberlin S, Evans JE, Darcey T, Aenlle K, Niedospial D, Mullan M, Crawford F, Klimas N, Abdullah L. Sex-specific plasma lipid profiles of ME/CFS patients and their association with pain, fatigue, and cognitive symptoms. J Transl Med. 2021 Aug 28;19(1):370. doi: 10.1186/s12967-021-03035-6.
- Background: PubMed 22392507Ruban A, Berkutzki T, Cooper I, Mohar B, Teichberg VI. Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas. Invest New Drugs. 2012 Dec;30(6):2226-35. doi: 10.1007/s10637-012-9799-5.
- Background: PubMed 27051598Swerdlow RH, Bothwell R, Hutfles L, Burns JM, Reed GA. Tolerability and pharmacokinetics of oxaloacetate 100 mg capsules in Alzheimer's subjects. BBA Clin. 2016 Mar 10;5:120-3. doi: 10.1016/j.bbacli.2016.03.005. eCollection 2016 Jun.
- Background: PubMed 32206660Tully L, Humiston J, Cash A. Oxaloacetate reduces emotional symptoms in premenstrual syndrome (PMS): results of a placebo-controlled, cross-over clinical trial. Obstet Gynecol Sci. 2020 Mar;63(2):195-204. doi: 10.5468/ogs.2020.63.2.195. Epub 2020 Feb 25.
- Background: PubMed 16448567Vernon SD, Whistler T, Cameron B, Hickie IB, Reeves WC, Lloyd A. Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus. BMC Infect Dis. 2006 Jan 31;6:15. doi: 10.1186/1471-2334-6-15.
- Oxaloacetate Acid Supplementation as a Mimic of Calorie RestrictionLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. At this time the IPD is not available to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suzanne D Vernon, Ph.D. principal investigator
Bateman Horne Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Medical Food - Anhydrous Enol-Oxaloacetate in people with Myalgic Encephalomyelitis and Chronic Fatigue Syndrome, run by Terra Biological LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction of Fatigue (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05273372, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.