REGAIN: RCT of Oxaloacetate for Fatigue in Long COVID

NCT05840237 | Completed DMC

• 1 other identifier: TB-2023-AEO LC
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Following acute COVID-19, some patients develop a group of debilitating symptoms that include fatigue, orthostatic intolerance, difficulty with attention and concentration (often called "brain fog"), myalgias and disrupted sleep. The term Long COVID is used to describe these symptoms after the initial viral infection has passed. These symptoms are the same as those that define myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A "Proof of Concept" trial showed significant fatigue benefit in Long COVID patients. This randomized, placebo controlled follow-on trial will determine whether oxaloacetate can reduce fatigue and improve other symptoms in patients with Long COVID who meet diagnostic criteria for ME/CFS.

Conditions

Post-COVID-19 Syndrome; Fatigue Syndrome, Chronic

Keywords

Long COVID; COVID; Fatigue; Oxaloacetate; COVID Fatigue

Outcome Measures

Primary Outcomes (1)

• Chalder Fatigue Score

  A Validated patient derived survey of fatigue

  42 days

Secondary Outcomes (2)

• Global Impression of Change

  42 days

• Up-Time

  42 days

Study Arms (2)

Oxaloacetate Arm

EXPERIMENTAL

1,000 mg of Anhydrous Enol-Oxaloacetate taken BID with Breakfast and Lunch

Other: Anhydrous Enol-Oxaloacetate, a "Medical Food"

Placebo Arm

PLACEBO COMPARATOR

1,000 mg of white Rice Flour taken BID with Breakfast and Lunch

Other: White Rice Flour

Interventions

Anhydrous Enol-Oxaloacetate, a "Medical Food" OTHER

Treatment with the medical food "Oxaloacetate CFS", 2 - 500 mg capsules BID with food

Also known as: Oxaloacetate, Oxaloacetate CFS

Oxaloacetate Arm

White Rice Flour OTHER

Treatment with the food "White Rice Flour", 2- 500 mg capsules BID with food

Also known as: Rice Flour

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form. Male or female, 18 to 65 years of age. Able to read, understand and voluntarily sign the informed consent form.
• Diagnosed with Long COVID by a provider after suspected, probable or confirmed infection with SARS-CoV-2 as defined by the WHO (see full protocol for details). Patients have experienced moderate to severe fatigue at least 50% of the time over the past 6 months that is not relieved by rest and post-exertional malaise (PEM) which is unusual worsening of symptoms after minimal physical or cognitive exertion, which can occur or persist 24 hours or more after the exertion.
• Agree to refrain from taking medications that would affect assessment of the effectiveness of study IP 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 be confirmed negative prior to dispensing IP. Women of child-bearing potential will have a urine pregnancy test at each visit (2 and 3) 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.
• Stated willingness to comply with all study procedures. Be available and appear for the 3 in-person visits of the study. Have mobile (smart) phone and access to the internet. Willingness to wear a device on their ankle.

You may not qualify if:

• Active or uncontrolled co-morbidities (including depression, untreated endocrine diagnoses), which may interfere with the ability of the patient to participate in the study in the opinion of the Principal Investigator or Sub-Investigator.
• Body Mass Index \>40 Known allergy to rice flour. Any investigational drug use in the past 30 days. Fatigue improvement because of a current treatment intervention. Treatment within the past 14 days or current treatment with stimulants including methylphenidate, amphetamine-dextroamphetamine, phentermine, lisdexamfetamine, modafinil, and armodafinil Previous or current use of oxaloacetate. 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.
• Past medical history of:
• Untreated or uncontrolled major depressive disorder, untreated or uncontrolled endocrine diagnoses including hypothyroidism (Hashimoto's, etc.), Grave's disease, adrenal insufficiency, hypogonadism (testosterone deficiency), diabetes mellitus or insipidus.
• In the last 3 years have they experienced a concussion with loss of consciousness, brain surgery, an automobile accident with head/neck injury, and/or other traumatic brain injury.
• Active 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 \< 90 mmHg or rested sitting diastolic BP \< 60 mmHg, Substance abuse in the past 12 months as determined by self-report or in the opinion of the PI and Sub-I

Sponsors & Collaborators

• Terra Biological LLC: lead
• Bateman Horne Center: collaborator

Study Sites (1)

Bateman Horne Center

Salt Lake City, Utah, 84102, United States

Location

Related Publications (1)

• Cash A, Kaufman DL. Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial. J Transl Med. 2022 Jun 28;20(1):295. doi: 10.1186/s12967-022-03488-3.

  PMID: 35764955 RESULT

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Fatigue Syndrome, Chronic; Fatigue

Interventions

Oxaloacetic Acid; Flour

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Oxaloacetates; Oxalates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Keto Acids; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Lucinda Bateman, MD

  Bateman Horne Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Individual patients will be randomized, and will receive a numbered bottle that corresponds to either Oxaloacetate or placebo. At the end of the trial, the blind will be broken to reveal which participant is in which group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Center, Randomized, Placebo Controlled, Double Blind

Study Record Dates

• First Submitted: April 28, 2023
• First Posted: May 3, 2023
• Study Start: June 1, 2023
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: February 4, 2025

Record last verified: 2024-11

Locations

US (1)