Effects of Pau d' Arco in Primary Dysmenorrhea

A single arm, open-label trial evaluating safety and tolerability of encapsulated Tabebuia avellanedae in 12 generally healthy women aged 18-45 with primary dysmenorrhea (PDM). This will be the first study evaluating the safety and tolerability of Tabebuia avellanedae in PDM. We also aim to collect proof-of-concept mechanistic data supporting the hypothesis that Tabebuia avellanedae reduces PGE2 concentration in vivo in women with PDM.

This is a single arm, open-label trial evaluating safety and tolerability of 1,050 mg/day of encapsulated Tabebuia avellanedae every day for 2 months, as well as effects of the treatment on quality of life, pain intensity, and pain interference, in 12 generally healthy women aged 18-45 with PDM. Outcomes of this study include questionnaires to evaluate: safety and tolerability using standardized adverse events scales (primary); participant reported measurements of quality of life, pain intensity, and pain interference around menses collected on validated instruments (secondary); and blood concentration of PGE2 and high-sensitivity C-reactive protein (tertiary). The protocol followed the SPIRIT guidelines and fulfilled the SPIRIT checklist.

Eligibility Criteria:
Inclusion Criteria:

* Biologically female
* Ages 18-45
* Presence of primary dysmenorrhea
* Has a 'smart' phone and is willing to download and use an electronic application for use during the study.
* Willing to take a non-hormonal form of birth control throughout the trial period (abstinence, condom, diaphragm, or copper IUD (ParaGard))
* Lives in the Portland area
* Able to speak, read and write English
* Has reliable transportation to clinic
* Willing to have four fasting blood draws taken
* Wiling to collect menstrual fluid in a Diva© cup on the first day of menstruation and ability to deliver it to the clinic on the same day
* Ability to receive and complete electronic VAS scales
* Pain scale rating of 6 or higher on the VAS scale
* Monthly pain that correlates with menstruation

Exclusion Criteria:

* Presence of secondary dysmenorrhea
* General health measures outside of normal range:

  * Blood pressure readings obtained at the Screening Visit reveal hypotension (≤90/60 mmHg) or hypertension (≥140/90 mmHg).
  * Aspartate aminotransferase (AST) \< 8 U/L or \> 48 U/L at the Screening Visit.
  * Alanine aminotransferase (AST) \< 7 U/L or \> 55 U/L at the Screening Visit.
  * Estimated glomerular filtration rate (eGFR) \< 90 ml/min/1.73m2 at the Screening Visit.
  * An INR value \> 1.1 at the Screening Visit.
  * A red blood cell count \< 3.90 million cells/mcL or \> 5.03 million cells/mcL.
  * A hemoglobin value of \< 12 g/dL (120 g/L) or \> 15.5 g/dL (155 g/L).
  * A hematocrit value of \< 34.9% or \> 44.5%.
  * A white blood cell count \< 3.5 billion cells/L (3,500 cells/mcL) or \> 10.5 billion cells/L (10,500 cells/mcL)
  * A platelet count \< 150 billion/L (150,000/mcL) or \> 450 billion/L (450,000 mcL).
* Women who are nursing, pregnant, or planning pregnancy in the next four months
* Difficulty swallowing or aversion to capsules, tablets, or pills
* Currently taking, and unwilling to discontinue, NSAIDs (Aspirin, Ibuprofen)
* Currently taking dietary supplements with any of the following ingredients in amounts over 250 mg/day: cinnamon, garlic, ginger, turmeric, and/or curcumin
* Consumption of \>1 alcoholic drink per day, during the study period
* Currently taking any anticoagulation medications (Warfarin/Coumadin)
* Currently taking, or have taken in the past two months, hormonal forms of birth control
* Unwillingness, or inability, to take a monthly pregnancy test during the timeline of the study (3 pregnancy tests)
* Past or present medical history of any of the following:

  * Blood clotting disorders (von Willebrand disease, Hemophilia A, Hemophilia B, etc.)
  * Liver disease (cirrhosis, hepatitis, liver failure, jaundice, liver cancer, etc.)
  * Kidney disease (chronic kidney disease, polycystic kidney disease, etc.)
  * Cardiac disease (hypertension, heart failure, cardiomyopathy, etc.)
  * Anemia (iron deficiency, sickle cell, aplastic, etc.)
  * Inflammatory bowel disease
  * Irritable bowel syndrome
  * Endometriosis
  * Obstructive endometrial polyps
  * Chronic pelvic inflammatory disease
  * Polycystic Ovarian Syndrome
  * Adenomyosis
  * Intrauterine or pelvic adhesions
  * Congenital obstructive mullerian malformations
  * Cervical stenosis
  * Use of an intrauterine contraceptive device that causes pain
  * Pelvic congestion syndrome
  * Reproductive cancer (uterine cancer, ovarian cancer, endometrial cancer, etc.)
  * Ovarian cysts
  * Fibroids
  * Uteropelvic junction obstruction