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REGAIN: RCT of Oxaloacetate for Fatigue in Long COVID

Primary Purpose

Post-COVID-19 Syndrome, Fatigue Syndrome, Chronic

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Anhydrous Enol-Oxaloacetate, a "Medical Food"
White Rice Flour
Sponsored by
Terra Biological LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post-COVID-19 Syndrome focused on measuring Long COVID, COVID, Fatigue, Oxaloacetate, COVID Fatigue

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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

Sites / Locations

  • Bateman Horne CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Oxaloacetate Arm

Placebo Arm

Arm Description

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

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

Outcomes

Primary Outcome Measures

Chalder Fatigue Score
A Validated patient derived survey of fatigue

Secondary Outcome Measures

Global Impression of Change
A Validated patient derived survey for overall improvment
Up-Time
Measurement of physical activity with a device attached to the ankle

Full Information

First Posted
April 28, 2023
Last Updated
May 18, 2023
Sponsor
Terra Biological LLC
Collaborators
Bateman Horne Center
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1. Study Identification

Unique Protocol Identification Number
NCT05840237
Brief Title
REGAIN: RCT of Oxaloacetate for Fatigue in Long COVID
Official Title
REGAIN: A Randomized, Double Blind, Placebo Controlled Trial to Determine the Effects of Oxaloacetate on Improving Fatigue in Long COVID
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2023 (Anticipated)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Terra Biological LLC
Collaborators
Bateman Horne Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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 (1-8). The term Long COVID is used to describe the prolonged multisystem illness that occurs after acute infection with SARS-CoV-2. The frequency with which this syndrome occurs following acute COVID-19 ranges from 2-40% of cases (8, 9). Although individuals with more severe acute COVID-19 are more likely to develop Long COVID, it is prevalent in people who were mildly symptomatic or asymptomatic at the time of acute infection with SARS-CoV-2 (8, 10, 11). Many people with Long COVID remain ill for many months. Currently there are thousands of people in the U.S. that have been suffering with Long COVID for the past three years since the onset of the COVID-19 pandemic in January 2020 (12). In a recent study, the Imperial College in London estimated that there are 2 million adults suffering from Long COVID in the UK (13). According to the US News, Long COVID has become the 'Pandemic After the Pandemic (14). There is evidence that diagnosis and treatment early in the course of illness improves the likelihood of recovery and sustained remission of post-infectious illness (15, 16). A code U09.9 was added to ICD-10 in October 2021 to document post-acute sequela of COVID-19 after infection and Long COVID. The WHO published a Long COVID clinical case definition coincident with the ICD code that described the common symptoms of Long COVID including fatigue, shortness of breath, cognitive dysfunction but also others and these generally have an impact on everyday functioning (17). The signs and symptoms described in this case definition were also described in survey responses from an international cohort of more than 6,000 people with Long COVID (18). This study found that signs and symptoms that persisted more than 6 months of illness included fatigue, brain fog, post-exertional malaise, insomnia, joint and muscle pain, orthostatic intolerance, gastrointestinal symptoms, and sensorimotor symptoms including tremors and nerve pain. These symptoms are the same as those that define myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is defined by the National Academy of Medicine as a substantial reduction or impairment in the ability to engage in pre-illness levels of activity (occupational, educational, social, or personal life) that lasts for more than 6 months and is accompanied by profound fatigue of new onset that is not a result of ongoing or unusual excessive exertion and is not alleviated by rest; post-exertional malaise (PEM) which is the worsening of symptoms after physical, mental, or emotional exertion that would not have caused a problem before the illness; unrefreshing sleep; and at least one of the following two additional manifestations must be present, cognitive impairment or orthostatic intolerance (18). Oxaloacetate is an energy metabolite found in every cell of the human body. It holds a key place in the TCA cycle within the mitochondria, providing energy to the cells. It is also a critical early metabolite in gluconeogenesis, which provides glucose for the heart and brain during times of low glucose. In addition, oxaloacetate is found in the urea cycle (which converts toxic ammonia to urea), amino acid synthesis, and fatty acid synthesis. It is critical to human metabolism and proper cellular function, and it is central to energy production and use in the body. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-COVID-19 Syndrome, Fatigue Syndrome, Chronic
Keywords
Long COVID, COVID, Fatigue, Oxaloacetate, COVID Fatigue

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Single Center, Randomized, Placebo Controlled, Double Blind
Masking
ParticipantCare ProviderInvestigator
Masking Description
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.
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Oxaloacetate Arm
Arm Type
Experimental
Arm Description
1,000 mg of Anhydrous Enol-Oxaloacetate taken BID with Breakfast and Lunch
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
1,000 mg of white Rice Flour taken BID with Breakfast and Lunch
Intervention Type
Other
Intervention Name(s)
Anhydrous Enol-Oxaloacetate, a "Medical Food"
Other Intervention Name(s)
Oxaloacetate, Oxaloacetate CFS
Intervention Description
Treatment with the medical food "Oxaloacetate CFS", 2 - 500 mg capsules BID with food
Intervention Type
Other
Intervention Name(s)
White Rice Flour
Other Intervention Name(s)
Rice Flour
Intervention Description
Treatment with the food "White Rice Flour", 2- 500 mg capsules BID with food
Primary Outcome Measure Information:
Title
Chalder Fatigue Score
Description
A Validated patient derived survey of fatigue
Time Frame
42 days
Secondary Outcome Measure Information:
Title
Global Impression of Change
Description
A Validated patient derived survey for overall improvment
Time Frame
42 days
Title
Up-Time
Description
Measurement of physical activity with a device attached to the ankle
Time Frame
42 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lucinda Bateman, MD
Phone
801-532-8311
Email
sdvernon@batemanhornecenter.org
First Name & Middle Initial & Last Name or Official Title & Degree
Candace Rond, CCRC
Phone
801-532-8311
Email
crond@batemanhornecenter.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lucinda Bateman, MD
Organizational Affiliation
Bateman Horne Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bateman Horne Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84102
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lucinda Bateman, MD
Phone
801-532-8311
Email
sdvernon@batemanhornecenter.org
First Name & Middle Initial & Last Name & Degree
Facility Manager
Phone
801-359-7400
Email
support@batemanhornecenter.org

12. IPD Sharing Statement

Citations:
PubMed Identifier
35764955
Citation
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.
Results Reference
result

Learn more about this trial

REGAIN: RCT of Oxaloacetate for Fatigue in Long COVID

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