Evaluating Changes in Microbiota Composition and Quality of Life in Irritable Bowel Syndrome: A Randomized, Controlled Trial
Principal Investigator: Ryan Bradley ND, MPH (NUNM)
Clinical Investigator: Nini Callan, ND, MS (NUNM)
Co-Investigator: Jamie Corroon, ND, MPH (NUNM), Mahmoud Ghannoum, PhD; Case Western Reserve University
Study Coordinator: Anders Gundersen, MS (NUNM)
This study is a two-arm, 1:1, randomized, double-blind, placebo-controlled clinical trial. The primary research question to be addressed in this investigation is as follows: Does a 2’-FL-containing dietary supplement impact stool microbiota composition in adults with IBS? The primary measure for determining potential impacts of the 2’-FL-containing dietary supplement on stool microbiota composition is stool abundance of Faecalibacterium prausnitzii, a commensal intestinal bacteria. Additional measures related to determining potential impacts of the 2’-FL-containing dietary supplement on gut microbiota composition are stool levels of additional commensal intestinal bacteria, measures of intestinal microbial diversity, Bristol Stool Form Scale changes, and IBS symptom questionnaires.
Primary Outcome Measure:
- F. prausnitzii abundance in stool
Secondary Outcome Measures:
- Relative abundance of F. prausnitzii in stool
- Relative abundance of Bifidobacterium spp. in stool
- Alpha diversity
- Beta diversity
- IBS-Severity Scoring System (IBS-SSS) score
- IBS-Adequate Relief from Symptoms (IBS-AR)
- Bristol Stool Form Scale (BSFS)
Exploratory Outcome Measures:
- Relative abundance of additional microbiota in stool
- Butyric acid
- Acetic acid
- Propionic acid
- Lactic acid
- Formic acid
- Valeric acid
Evaluating changes in Epigenetic Methylation from Antiorbital Ionic Calcium in Adults with Atrial Fibrillation (AIC-AF)
Principal Investigators: Ryan Bradley ND, MPH, (NUNM)
Co-Investigators: Paul Lee, PhD, Calcium Bone Health Institute (CBHI), Jamie Corroon, ND, MPH, (NUNM), Nini Callan, ND, MS, (NUNM), Joseph Aslan, PhD, (OHSU)
Biostatistician: Jamie Corroon, ND, MPH, (NUNM)
Study Coordinator: Anders Gundersen, MS (NUNM)
The overarching objectives are to assess mechanistic, epigenetic effects, general clinical tolerance, and adverse effects of an ionized calcium dietary supplement, as compared to placebo, using a randomized, placebo-controlled design for 12 weeks, and during a subsequent open-label, follow-up design for an additional 12 weeks, in individuals with atrial fibrillation.
Primary outcome measure: Rate of aging using the Dunedin (P)ace of (A)ging (C)alculated from the (E)pigenome (i.e., DunedinPACE) epigenetic “speedometer”.
Secondary outcome measure: Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT)
Tertiary outcome measures:
- Serum ionic calcium – Quest Diagnostic’s Serum Ionic Calcium.
- Frequency of fibrillation episodes – KardiaMobile mobile ECG device
- Calcification of the coronary arteries – Coronary Artery Calcium score as measured by computerized tomography (optional).
- Bone Densitometry: BeamMed Ltd’s Sunlight MiniOmni Portable Bone Density Scanner; Rayus Radiology DEXA scan (optional).
- Bone formation and turnover studies – Quest Diagnostics Inc.’s serum Calcitonin, Osteocalcin, bone-specific Alkaline Phosphatase, Procollagen Type I Intact N Terminal Propeptide (PINP), and Collagen Type I C-Telopeptide (CTx).
- Clinical coagulation studies – Quest Diagnostics Inc.’s Prothrombin with INR and Partial Thromboplastin Times
- Clinical chemistry studies – Quest Diagnostics Inc.’s Comprehensive Metabolic Panel and Complete Blood Count
- Traditional Cardiovascular risk assessment – Quest Diagnostics Inc.’s Standard Lipid Panel
- C-reactive Protein (CRP)
- Thyroid screen – Quest Diagnostics Inc.’s Thyroid Stimulating Hormone (TSH).
- Platelet assessment — Blood drawn at NUNM into two sodium citrate-prepared vials, analyzed at Dr. Aslan’s OHSU lab.
- Adverse effects: NUNM Adverse Event Monitoring Form
Evaluating Changes in Quality of Life and Digestion in Functional Dyspepsia in Adults (QOL- FD)
Principal Investigators: Ryan Bradley ND, MPH, (NUNM)
Clinical Investigator and Co-Investigator: Jamie Corroon, ND, MPH, (NUNM)
Co-Investigator: Mahmoud Ghannoum, PhD; Case Western Reserve University
This study is a 5-week, randomized, triple-blinded, placebo-controlled clinical trial including a 1-week placebo run-in period (i.e., 1 week between enrollment and randomization) and two 4-day controlled feeding periods (i.e., week 1 and week 5). It will investigate the use of a dietary supplement (i.e., Zypan®) containing a proprietary formula of plant and animal-based ingredients over 4 weeks in individuals with Functional Dyspepsia. Participants will be randomized to either: intervention (i.e., Zypan®) or placebo three times daily before meals for 4 weeks.
Xanthohumol Microbiome and Signature in Healthy Adults
Principal Investigators: Ryan Bradley, ND, MPH (NUNM), Jan Frederik Stevens, PhD (OSU), Thomas Metz, PhD (PNNL)
This research is a collaboration between Oregon State University, Pacific Northwest National Laboratory and NUNM. Funded by the National Institutes of Health, this randomized, triple-blind, placebo-controlled trial is designed to assess the impact of Xanthohumol (XN) on gut health. Evidence suggests XN, a polyphenolic compound found in hops, may reduce inflammation in Inflammatory Bowel Disease by reducing gut permeability and increasing the absorption of bile salts. This data will be compared with a subsequent phase two trial in adults with Crohn’s Disease.
This study is currently recruiting participants. For more information please visit here.
Effects of Pau d’ Arco on Primary Dysmenorrhea
Principal Investigator: Ryan Bradley, ND, MPH
Student Investigator: Christine McClure
This study will be the first study evaluating the tolerability of Tabebuia avellanedae in primary dysmenorrhea (PDM), experienced by up to 90% of menstruating women in the U.S. Tabebuia avellanedae is a South American tree, the inner bark of which has great potential as a candidate treatment for PDM This is a single arm, open-label trial evaluating safety and tolerability of 1,050 mg/day of encapsulated Tabebuia avellanedae for two 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.
Effects Of A Herbal/Homeopathic Combination Topical Salve On Cutaneous Oxygenation
Principal Investigators: Andrew Erlandsen, ND, Douglas Hanes, PhD, and Ryan Bradley ND, MPH
The purpose of this study was to assess the effects of the Puremedy Original Healing Salve on lower extremity cutaneous oxygen delivery measured as changes in transcutaneous oxygen pressure (TcP02). The salve includes 1x homeopathic dilutions of Calendula, Echinacea, and Sambucus extracts, plus extracts from pine and Balsam fir,
The study was a randomized, triple-masked, crossover trial in people with type 2 diabetes without peripheral artery disease. Participants were assigned in random order to receive either the Original Healing Salve or the salve base alone (control). After a 20-minute warm up cycle, the salve was applied and oximeter readings were recorded from four sensors, two on the lower leg and two on the foot at 5 minute intervals for 30 minutes. The primary study outcome was the difference in TcPO2 in the lower leg sensors between the test and control salves at 30 minutes after application. The secondary outcome was change in TcPO2 in the leg sensors from the application of the test salve. Exploratory analyses evaluated changes in TcPO2 at all time points and assessed for trends over time.
Sixteen participants with type 2 diabetes were randomized, and completed the trial. The mean difference in TcPO2 at 30 minutes in the leg sensors combined = 0.39 +/- 8.54, p = 0.86. Within the test group, the mean change in TcPO2 at 30 minutes in the leg sensors = 3.70 +/- 6.62, p = 0.04. There were no significant differences between the test and control salves at any time point. Significant linear and cubic trends were measured in both treatment groups, suggesting increases in TcPO2 over time. The Original Healing Salve increased TcPO2 after 30 minutes in people with type 2 diabetes, however the contribution of the herbal and homeopathic ingredients remain unclear.
Access the published paper here: https://www.ncbi.nlm.nih.gov/pubmed/30767637
Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study
Principal Investigator: Jenn Ryan, ND
Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults.
This single-arm, open-label pilot study included twelve hypercholesterolemic participants recruited into the study; one dropped out. Participants took 5.6×10(10) colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period.
Study outcome measures were fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) as measured at baseline, after 4 weeks, and after 8 weeks.
Eight weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease. Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the study period. The remaining outcome measures were not significantly altered.
Access the published paper here: https://www.ncbi.nlm.nih.gov/pubmed/25893960
Effects of MSM on Markers of Oxidative Stress and Muscle Damage Following Exhaustive Exercise
Kim Tippens, ND, MSAOM, MPH
Student Investigator: Eric Withee, MS
Exercise is an important component of improving and maintaining health. It helps maintain a healthy weight, strengthens muscle and bones, and can reduce the risk of many diseases. Highly exhaustive bouts of exercise, common during training and participation in competitive events, can instead have harmful effects. Exhaustive exercise produces high levels of reactive oxygen and nitrogen species (RONS) that react with and damage cells. The result is muscle damage associated with oxidative stress, as well as increased soreness and longer recovery times.
This study investigated the effect of methylsulfonylmethane (MSM) supplementation on post-exercise levels of oxidative stress. Twenty-two participants supplemented with either MSM or placebo for three weeks before competing in a half marathon. Researchers investigated whether MSM can reduce the levels oxidative stress, muscle damage and pain associated with exhaustive exercise by comparing post-race biomarker levels to pre-race levels.
As predicted, participation in a half-marathon was associated with increased oxidative-stress, muscle damage and pain. Results indicated that MSM supplementation may reduce exercise-induced muscle and joint pain, but results were not statistically significant. Further research on a larger sample size is warranted to determine whether MSM is useful in reducing pain and oxidative stress as a result of exhaustive exercise.
Access the published paper here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5521097/
Prospective Safety and Tolerability Assessment of a Cardiovascular Health Dietary Supplement (Carditone)
Principal Investigators: Ryan Bradley ND, MPH & Jenn Ryan ND, MS
Hypertension is an important overall risk factor for developing cardiovascular disease in the United States, and is a leading risk factor for cardiovascular events. Carditone™ is a dietary supplement intended to support healthy blood pressure levels and cardiovascular health. Carditone™ has been on the market for over 20 years and no adverse events related to its use have been reported. However, prospective safety data and physiological measures of end organ function have not previously been collected or reported. This is the first study evaluating the safety and tolerability of Carditone™.
This study assessed the safety and tolerability of one daily tablet of Carditone™ by questionnaire and blood markers in adults with borderline to mild hypertension over a 6 month period. Thirty men and women with blood pressure readings consistent with criteria for pre‐hypertension or stage I hypertension were recruited. Outcome measures were collected at baseline, 3 months, and 6 months; these measures included questionnaires to monitor for potential side effects and adverse events, changes in mood and sleep quality, as well as blood markers that monitor cardiovascular, liver, and kidney function. In addition, safety was assessed by monthly phone calls and at any time by spontaneous self‐report.
Results show that most of the physiological measures of organ function and health did not change. However, potassium levels increased, while both systolic and diastolic blood pressure decreased. There were no serious adverse events; however, 30% of participants withdrew citing potential side effects. The findings suggest that the dietary supplement, Carditone™, is safe for long-term use in adults with prehypertension and stage I hypertension. The increase in potassium and decreases in blood pressure are promising and suggest that future research on this dietary supplement, or its ingredients, should further explore effects on blood pressure and biologic mechanisms of action.
Access the published paper here: https://www.liebertpub.com/doi/pdf/10.1089/acm.2018.0311
Epigenetics in Clinical Practice: Characterizing Patient and Provider Experiences with MTHFR Polymorphisms and Methylfolate
Principal Investigators: Erica Oberg, ND & Ryan Bradley ND, MPH
Abstract: Wide availability of genetic testing and increasing consumer demand for personalized medicine has lead to an increase in the diagnosis of genetic polymorphisms. One of the most commonly tested genes is MTHFR. This gene has been implicated in numerous medical conditions ranging from depression to autism to increased risk of cancer and cardiovascular disease.
Pharmacogenetics is the area of medicine that is evolving to treat genetic polymorphisms. In the case of MTHFR polymorphisms, treatment with methylated forms of folate bypasses the defect on folic acid metabolism, supplying the patient with usable methylfolate that participates in numerous metabolic pathways that involve methylation. These critical pathways range from DNA synthesis to detoxification to blood clotting to fetal development in utero.
Because treatment with methylfolate is recommended based on lab testing for MTHFR polymorphisms rather than solely being based clinical expertise, we hypothesize that people may have unique experiences that warrant reporting in the literature. For example, patients may feel relief at having a therapeutic option to compensate for the polymorphism. Doctors may have unique insights into clinical situations that respond to methylfolate treatment that were previously unresponsive to folic acid. No reports of adverse events have been made in the literature; we will specifically ask about adverse events to address this knowledge gap.
Access the published paper here: https://www.ncbi.nlm.nih.gov/pubmed/26484755
Influence of an Omega-3 SPM Supplement on Quality of Life
Principal Investigator: Morgan Schafer, MS
One third of the America population is affected by chronic pain. The societal cost associated with chronic pain is up to $635 billion dollars annually. Prescribed pain medications may have negative side effects or cause addictions. Having alternative treatments that can reduce inflammation and the side effects associated with chronic pain may improve quality of life for millions of individuals afflicted with chronic pain.
This prospective, non-randomized, open-label study assessed if taking an Omega-3 SPM™ softgel supplement for four weeks changed the quality of life in adults with chronic pain. SPM™ softgels are a dietary supplement intended to reduce pain and inflammation. Outcome measures were collected at baseline, 2 weeks, and 4 weeks with a primary endpoint of 4 weeks. The primary outcomes of this pilot study included questionnaires to assess quality of life. Exploratory outcomes assessed safety and tolerability, changes in anxiety and depression as well as levels of pain and blood markers associated with inflammation. Study results are pending publication.