Clinical trial NCT04245540: Effects of Pau d' Arco in Primary Dysmenorrhea
Official title: A Single Arm, Open-label Pilot Trial Examining the Effects of Pau d' Arco on Primary Dysmenorrhea in Reproductive Age Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Primary Dysmenorrhea
Keywords: primary dysmenorrhea
dysmenorrhea
tabebuia avellanedae
tabebuia impetiginosa
pau d' arco
taheebo bark
menstrual pain
pelvic pain
menstrual cramps
painful menstruation
menstrual distress
herbal medicine
phytomedicine
complementary therapy
complementary medicine
alternative therapy
alternative medicine
traditional medicine
plant extracts
supplement
Lead sponsor: National University of Natural Medicine
Sponsor class: OTHER
First posted: 2020-01-29
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm, open-label trial evaluating safety and tolerability.
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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

Primary outcomes:
measure: Red Blood Cell Count
timeFrame: Mean change in Screening RBC count to 4 weeks.
measure: Red Blood Cell Count
timeFrame: Mean change in Screening RBC count to 8 weeks.
measure: Red Blood Cell Count
timeFrame: Mean change in 4 weeks RBC count to 8 weeks.
measure: Hemoglobin
timeFrame: Mean change in Screening Hemoglobin g/dL to 4 weeks.
measure: Hemoglobin
timeFrame: Mean change in Screening Hemoglobin g/dL to 8 weeks.
measure: Hemoglobin
timeFrame: Mean change in 4 weeks Hemoglobin g/dL to 8 weeks.
measure: Hematocrit
timeFrame: Mean change in Screening Hematocrit % to 4 weeks.
measure: Hematocrit
timeFrame: Mean change in Screening Hematocrit % to 8 weeks.
measure: Hematocrit
timeFrame: Mean change in 4 weeks Hematocrit % to 8 weeks.
measure: Mean Corpuscular Volume
timeFrame: Mean change in Screening MCV fL to 4 weeks.
measure: Mean Corpuscular Volume
timeFrame: Mean change in Screening MCV fL to 8 weeks.
measure: Mean Corpuscular Volume
timeFrame: Mean change in 4 weeks MCV fL to 8 weeks.
measure: Mean Corpuscular Hemoglobin
timeFrame: Mean change in Screening MCH pg to 4 weeks.
measure: Mean Corpuscular Hemoglobin
timeFrame: Mean change in Screening MCH pg to 8 weeks.
measure: Mean Corpuscular Hemoglobin
timeFrame: Mean change in 4 weeks MCH pg to 8 weeks.
measure: Mean Corpuscular Hemoglobin Concentration
timeFrame: Mean change in 4 weeks MCH pg to 8 weeks.
measure: Recruitment and retention.
timeFrame: Percent change from Baseline Recruitment to 8 weeks.
measure: Incidence of Intervention-attributable Adverse Events
timeFrame: Percent change from Baseline Intervention-attributable Adverse Events to 4 weeks.
measure: Incidence of Intervention-attributable Adverse Events
timeFrame: Percent change from Baseline Intervention-attributable Adverse Events to 8 weeks.
measure: Incidence of Intervention-attributable Adverse Events
timeFrame: Percent from 4 weeks Intervention-attributable Adverse Events to 8 weeks.
measure: Aspartate aminotransferase (AST)
timeFrame: Mean change in Screening AST values at 4 weeks.
measure: Aspartate aminotransferase (AST)
timeFrame: Mean change in Screening AST values at 8 weeks.
measure: Aspartate aminotransferase (AST)
timeFrame: Mean change in 4 weeks AST values at 8 weeks.
measure: Alanine aminotransferase (ALT)
timeFrame: Mean change in Screening ALT values at 4 weeks.
measure: Alanine aminotransferase (ALT)
timeFrame: Mean change in Screening ALT values at 8 weeks.
measure: Alanine aminotransferase (ALT)
timeFrame: Mean change in 4 weeks ALT values at 8 weeks.
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: Mean change in Screening eGFR value at 4 weeks.
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: Mean change in Screening eGFR value at 8 weeks.
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: Mean change in 4 weeks eGFR value at 8 weeks.
measure: International normalized ratio
timeFrame: Mean change in Screening INR value at 4 weeks.
measure: International normalized ratio
timeFrame: Mean change in Screening INR value at 8 weeks.
measure: International normalized ratio
timeFrame: Mean change in 4 weeks INR value at 8 weeks.
measure: Systolic Blood pressure
timeFrame: Mean change from Baseline systolic blood pressure at 4 weeks.
measure: Systolic Blood pressure
timeFrame: Mean change from Baseline systolic blood pressure at 8 weeks.
measure: Systolic Blood pressure
timeFrame: Mean change from 4 weeks systolic blood pressure at 8 weeks.
measure: Diastolic Blood pressure
timeFrame: Mean change from Baseline diastolic blood pressure at 4 weeks.
measure: Diastolic Blood pressure
timeFrame: Mean change from Baseline diastolic blood pressure at 8 weeks.
measure: Diastolic Blood pressure
timeFrame: Mean change from 4 weeks diastolic blood pressure at 8 weeks.
Secondary outcomes:
measure: Anxiety Subscore Patient Reported Outcomes Measurement Information System 29 (PROMIS-29)
timeFrame: Mean change in Baseline Anxiety Score and 8 weeks.
measure: Depression Subscore of the Patient Reported Outcomes Measurement Information System 29 (PROMIS-29)
timeFrame: Mean change in Baseline Depression Score and 8 weeks.
measure: Fatigue Subscore of the Patient Reported Outcomes Measurement Information System 29 (PROMIS-29)
timeFrame: Mean change in Baseline Fatigue Score and 8 weeks.
measure: Pain Interference Subscore of the Patient Reported Outcomes Measurement Information System 29 (PROMIS-29)
timeFrame: Mean change in Baseline Pain Interference Score and 8 weeks.
measure: Sleep Disturbance Subscore of the Patient Reported Outcomes Measurement Information System 29 (PROMIS-29)
timeFrame: Mean change in Baseline Sleep Disturbance Score and 8 weeks.
measure: Physical Functioning Subscore of the Patient Reported Outcomes Measurement Information System 29 (PROMIS-29)
timeFrame: Mean change in Baseline Physical Functioning Score and 8 weeks.
measure: Social Role Subscore of the Patient Reported Outcomes Measurement Information System 29 (PROMIS-29)
timeFrame: Mean change in Baseline Social Role Score and 8 weeks.
measure: Visual Analog Scale (VAS)
timeFrame: Mean change in Baseline VAS Score and 4 weeks.
measure: Visual Analog Scale (VAS)
timeFrame: Mean change in Baseline VAS Score and 8 weeks.
measure: Visual Analog Scale (VAS)
timeFrame: Mean change in 4 weeks VAS Score and 8 weeks.
measure: Patient Reported Outcomes Measurement Information System (PROMIS) Sexual Function Measure
timeFrame: Mean change in Baseline PROMIS Sexual Function Score and 8 weeks.
Other outcomes:
measure: High sensitivity C-reactive protein (hs-CRP)
timeFrame: Mean change in Baseline hs-CRP and 8 weeks.
measure: Prostaglandins
timeFrame: Mean change in Baseline prostaglandin levels and 8 weeks
Locations:
city: Portland
country: United States
facility: National University of Natural Medicine
state: Oregon
Study officials:
affiliation: National University of Natural Medicine
name: Ryan Bradley, ND, MPH
role: PRINCIPAL_INVESTIGATOR
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