Clinical trial NCT03509714: Oxaloacetate Supplementation for Emotional PMS
Official title: Oxaloacetate Supplementation for Emotional PMS; Measuring Improvements in Depression, Anxiety, Perceived Stress, and Aggression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Premenstrual Syndrome (PMS)
Lead sponsor: Terra Biological LLC
Sponsor class: INDUSTRY
First posted: 2018-04-26
Enrollment: 48
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Depression associated with Emotional PMS
timeFrame: 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).
measure: Anxiety associated with Emotional PMS
timeFrame: 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).
measure: Perceived Stress with Emotional PMS
timeFrame: 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).
measure: Aggression with Emotional PMS
timeFrame: 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).
measure: Adverse Event Reporting
timeFrame: Through study completion, an average of 60 days (2 menstrual cycles)
Secondary outcomes:
measure: Suicidal Ideation with Emotional PMS
timeFrame: 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).
Other outcomes:
Locations:
Study officials:
affiliation: Energy Medicine research Institute
name: Lisa Tully, PhD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.