Clinical trial NCT05273372: RESTORE ME -- RCT of Oxaloacetate on Improving Fatigue in ME/CFS
Official title: A Randomized Double Blind Placebo Controlled Trial to Determine the Effects of Oxaloacetate on Improving Fatigue in ME/CFS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Myalgic Encephalomyelitis
Chronic Fatigue Syndrome
Fatigue
Lead sponsor: Terra Biological LLC
Sponsor class: INDUSTRY
Collaborators: name: Bateman Horne Center
First posted: 2022-03-10
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Placebo-controlled double blinded 2 arm study. 40 patients in treatment arm, 40 patients in placebo arm.
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: Inclusion Criteria:

* 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
  * 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

Exclusion Criteria:

* 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
  * 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

Primary outcomes:
measure: Reduction of Fatigue
timeFrame: 90 days
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 90 days
measure: Physical Functioning on the SF-36
timeFrame: 90 days
measure: Patient Global Impression of Change Questionnaire, 7 point scale, -3 to +3, with the higher score indicating more improvement
timeFrame: 90 days
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: Bateman Horne Center
state: Utah
Study officials:
affiliation: Bateman Horne Center
name: Suzanne D Vernon, Ph.D.
role: PRINCIPAL_INVESTIGATOR
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