REGAIN: RCT of Oxaloacetate for Fatigue in Long COVID

Prior treatment

• Exclusion Criteria Alternate medical or psychiatric illness that explains Long COVID symptoms in the opinion of the Investigator or sub-investigator.
  • 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

• 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.