Oxaloacetate Supplementation for Emotional PMS (OAA4PMS)
Primary Purpose
Premenstrual Syndrome (PMS)
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Jubilance (100 mg Oxaloacetate/150 mg Ascorbic Acid)
rice flour (Placebo)
Sponsored by
About this trial
This is an interventional treatment trial for Premenstrual Syndrome (PMS)
Eligibility Criteria
Inclusion Criteria:
- Women with Emotional Premenstrual Syndrome (PMS),
- Women who speak English as their primary language
- Women who understand the Human Consent Form
- Ability to swallow capsules
Exclusion Criteria:
- Formal diagnosis of clinical depression
- Formal diagnosis of premenstrual dysphoric disorder (PMDD).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Experimental: Part 1 Oxaloacetate Random
Experimental: Part 2 Oxaloacetate Second
Arm Description
Participants take 2 capsules Jubilance 100 mg Oxaloacetate/150 mg Ascorbic Acid blend per day during their entire menstrual cycle (approximately 28 days) or 2 capsules of 250 mg rice flour (Placebo). After one menstrual cycle, they cross-over to the other option.
Participants take 2 capsules of 250 mg rice flour (Placebo) per day during their entire menstrual cycle (approximately 28 days). After one menstrual cycle, they cross-over to 2 capsules of Jubilance 100 mg Oxaloacetate/150 mg Ascorbic Acid blend.
Outcomes
Primary Outcome Measures
Depression associated with Emotional PMS
Depression as measured during Emotional PMS with Beck's Depression Inventory Survey, which scores depression with 26 questions rated 0 to 3. Total score ranges from 0 to 78. Higher values indicate worse depression.
Anxiety associated with Emotional PMS
Anxiety as measured during Emotional PMS with Generalized Anxiety Disorder Survey, which scores anxiety with 7 questions rated 0 to 3. Total score ranges from 0 to 21. Higher values indicate worse anxiety.
Perceived Stress with Emotional PMS
Perceived Stress as measured during Emotional PMS with Cohen's Perceived Stress Survey, which scores perceived stress with 9 questions rated 0 to 4. Total score ranges from 0 to 36. Higher values indicate worse perceived stress.
Aggression with Emotional PMS
Aggression as measured during Emotional PMS with Buss-Perry Aggression Scale, which scores depression with 29 questions rated 1 to 5. Total score ranges from 29 to 145. Higher values indicate worse aggression.
Adverse Event Reporting
Safety of oxaloacetate supplementation in Emotional PMS patients
Secondary Outcome Measures
Suicidal Ideation with Emotional PMS
Suicidal Ideation as measured with a subscale of Beck's Depression Inventory, with a scale ranging from 0 to 3 in women who initially record suicidal ideation of greater than 0.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03509714
Brief Title
Oxaloacetate Supplementation for Emotional PMS
Acronym
OAA4PMS
Official Title
Oxaloacetate Supplementation for Emotional PMS; Measuring Improvements in Depression, Anxiety, Perceived Stress, and Aggression
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
October 17, 2016 (Actual)
Primary Completion Date
September 1, 2017 (Actual)
Study Completion Date
September 1, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Terra Biological LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Emotional Premenstrual Syndrome (PMS) affects millions of women worldwide. For Emotional PMS, including depression, anxiety, perceived stress and aggression, there are very few options. Recent observational data suggest that nutritional supplementation with oxaloacetate, a human energy metabolite, greatly reduced the symptoms of Emotional PMS. The aim of this study was to confirm these observations on the effects of oxaloacetate on Emotional PMS symptom severity within a controlled clinical trial setting.
Detailed Description
Oxaloacetate is an energy metabolite found in every cell of the human body. It holds a key place in the Krebs 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. It is critical to human metabolism, proper cellular function and it is central to energy production and use in the body.
Oxaloacetate may affect Emotional PMS through multiple mechanisms. During PMS, there is a large increase in glucose utilization in the cerebellum of the brain in women who are affected with emotional mood swings. Oxaloacetate supplementation has been shown to support proper glucose levels in the body. Having an excess of oxaloacetate allows gluconeogenesis take place upon demand, thereby fueling the brain, and perhaps meeting cerebellum glucose need.
In addition to oxaloacetate's ability to support proper glucose regulation, oxaloacetate affects two chemicals in the brain, GABA and glutamate. Altering the GABA/Glutamate ratio can affect mood. Oxaloacetate supplementation can reduce glutamate levels in the brain via a process called "Glutamate Scavenging". In addition, oxaloacetate supplementation was shown to increase GABA levels in animal models. By both lowering glutamate and increasing GABA, the GABA/Glutamate ratio is affected, which may also help women with Emotional PMS.
This study will investigate oxaloacetate's effect on Emotional PMS using patient completed surveys to measure depression, anxiety, perceived stress, and aggression, and statistically compare these results against placebo (rice flour) and baseline measurements.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Premenstrual Syndrome (PMS)
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Baseline measurement of all participants. Randomized double-blinded placebo controlled crossover study for Phase 1. Due to carry-over effects, Phase 2 of the study started each participant with placebo.
Masking
ParticipantCare ProviderInvestigator
Masking Description
Oxaloacetate/Vitamin C capsules were bottled in 30 count HDPE bottles. Placebo capsules (rice flour) were manufactured to similar size capsules and bottles. Bottles were labeled either Group A or Group 1. Code was broken at the end of Phase 1 of the study.
Allocation
Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental: Part 1 Oxaloacetate Random
Arm Type
Active Comparator
Arm Description
Participants take 2 capsules Jubilance 100 mg Oxaloacetate/150 mg Ascorbic Acid blend per day during their entire menstrual cycle (approximately 28 days) or 2 capsules of 250 mg rice flour (Placebo). After one menstrual cycle, they cross-over to the other option.
Arm Title
Experimental: Part 2 Oxaloacetate Second
Arm Type
Active Comparator
Arm Description
Participants take 2 capsules of 250 mg rice flour (Placebo) per day during their entire menstrual cycle (approximately 28 days). After one menstrual cycle, they cross-over to 2 capsules of Jubilance 100 mg Oxaloacetate/150 mg Ascorbic Acid blend.
Intervention Type
Dietary Supplement
Intervention Name(s)
Jubilance (100 mg Oxaloacetate/150 mg Ascorbic Acid)
Other Intervention Name(s)
Jubilance for Emotional PMS
Intervention Description
2 Pills to be taken orally per day during their entire menstrual cycle
Intervention Type
Dietary Supplement
Intervention Name(s)
rice flour (Placebo)
Intervention Description
250 mg rice flour (Placebo)
Primary Outcome Measure Information:
Title
Depression associated with Emotional PMS
Description
Depression as measured during Emotional PMS with Beck's Depression Inventory Survey, which scores depression with 26 questions rated 0 to 3. Total score ranges from 0 to 78. Higher values indicate worse depression.
Time Frame
Change from baseline value to value after supplementation for entire menstrual cycle (about 28 days) for each study arm in cross-over design (3 data points compared 1 at baseline 1 after menstrual cycle 1 and 1 after menstrual cycle 2).
Title
Anxiety associated with Emotional PMS
Description
Anxiety as measured during Emotional PMS with Generalized Anxiety Disorder Survey, which scores anxiety with 7 questions rated 0 to 3. Total score ranges from 0 to 21. Higher values indicate worse anxiety.
Time Frame
Change from baseline value to value after supplementation for one entire menstrual cycle (about 28 days) for each study arm in cross-over design (3 data points compared 1 at baseline 1 after menstrual cycle 1 and 1 after menstrual cycle 2).
Title
Perceived Stress with Emotional PMS
Description
Perceived Stress as measured during Emotional PMS with Cohen's Perceived Stress Survey, which scores perceived stress with 9 questions rated 0 to 4. Total score ranges from 0 to 36. Higher values indicate worse perceived stress.
Time Frame
Change from baseline value to value after supplementation for one entire menstrual cycle (about 28 days) for each study arm in cross-over design (3 data points compared 1 at baseline 1 after menstrual cycle 1 and 1 after menstrual cycle 2).
Title
Aggression with Emotional PMS
Description
Aggression as measured during Emotional PMS with Buss-Perry Aggression Scale, which scores depression with 29 questions rated 1 to 5. Total score ranges from 29 to 145. Higher values indicate worse aggression.
Time Frame
Change from baseline value to value after supplementation for one entire menstrual cycle (about 28 days) for each study arm in cross-over design (3 data points compared 1 at baseline 1 after menstrual cycle 1 and 1 after menstrual cycle 2).
Title
Adverse Event Reporting
Description
Safety of oxaloacetate supplementation in Emotional PMS patients
Time Frame
Through study completion, an average of 60 days (2 menstrual cycles)
Secondary Outcome Measure Information:
Title
Suicidal Ideation with Emotional PMS
Description
Suicidal Ideation as measured with a subscale of Beck's Depression Inventory, with a scale ranging from 0 to 3 in women who initially record suicidal ideation of greater than 0.
Time Frame
Change from baseline value to value after supplementation for one entire menstrual cycle (about 28 days) for each study arm in cross-over design (3 data points compared 1 at baseline 1 after menstrual cycle 1 and 1 after menstrual cycle 2).
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Women with Emotional Premenstrual Syndrome (PMS),
Women who speak English as their primary language
Women who understand the Human Consent Form
Ability to swallow capsules
Exclusion Criteria:
Formal diagnosis of clinical depression
Formal diagnosis of premenstrual dysphoric disorder (PMDD).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lisa Tully, PhD
Organizational Affiliation
Energy Medicine research Institute
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
19793063
Citation
Williams DS, Cash A, Hamadani L, Diemer T. Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway. Aging Cell. 2009 Dec;8(6):765-8. doi: 10.1111/j.1474-9726.2009.00527.x. Epub 2009 Sep 30.
Results Reference
background
PubMed Identifier
4884771
Citation
Yoshikawa K. Studies on the anti-diabetic effect of sodium oxaloacetate. Tohoku J Exp Med. 1968 Oct;96(2):127-41. doi: 10.1620/tjem.96.127. No abstract available.
Results Reference
background
PubMed Identifier
21092938
Citation
Rapkin AJ, Berman SM, Mandelkern MA, Silverman DH, Morgan M, London ED. Neuroimaging evidence of cerebellar involvement in premenstrual dysphoric disorder. Biol Psychiatry. 2011 Feb 15;69(4):374-80. doi: 10.1016/j.biopsych.2010.09.029. Epub 2010 Nov 18.
Results Reference
background
PubMed Identifier
20821056
Citation
Schmahmann JD. The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychol Rev. 2010 Sep;20(3):236-60. doi: 10.1007/s11065-010-9142-x. Epub 2010 Sep 7.
Results Reference
background
PubMed Identifier
25027327
Citation
Wilkins 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.
Results Reference
background
PubMed Identifier
32206660
Citation
Tully 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.
Results Reference
derived
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Oxaloacetate Supplementation for Emotional PMS
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