Absorption Kinetics of Berberine and Dihydroberberine and Their Impact on Glycemia: A Randomized, Controlled, Crossover Pilot Trial

Berberine is a natural alkaloid used to improve glycemia but displays poor bioavailability and increased rates of gastrointestinal distress at higher doses. Recently, dihydroberberine has been developed to combat these challenges. This study was designed to determine the rate and extent to which berberine appeared in human plasma after oral ingestion of a 500 mg dose of berberine (B500) or 100 mg and 200 mg doses of dihydroberberine (D100 and D200). In a randomized, double-blind, crossover fashion, five males (26 ± 2.6 years; 184.2 ± 11.6 cm; 91.8 ± 10.1 kg; 17.1 ± 3.5% fat) completed a four-dose supplementation protocol of placebo (PLA), B500, D100, and D200. The day prior to their scheduled visit, participants ingested three separate doses with breakfast, lunch, and dinner. Participants fasted overnight (8–10 h) and consumed their fourth dose with a standardized test meal (30 g glucose solution, 3 slices white bread) after arrival. Venous blood samples were collected 0, 20, 40, 60, 90, and 120 minutes (min) after ingestion and analyzed for BBR, glucose, and insulin. Peak concentration (CMax) and area under the curve (AUC) were calculated for all variables. Baseline berberine levels were different between groups (p = 0.006), with pairwise comparisons indicating that baseline levels of PLA and B500 were different than D100. Berberine CMax tended to be different (p = 0.06) between all conditions. Specifically, the observed CMax for D100 (3.76 ± 1.4 ng/mL) was different than PLA (0.22 ± 0.18 ng/mL, p = 0.005) and B500 (0.4 ± 0.17 ng/mL, p = 0.005). CMax for D200 (12.0 ± 10.1 ng/mL) tended (p = 0.06) to be different than B500. No difference in CMax was found between D100 and D200 (p = 0.11). Significant differences in berberine AUC were found between D100 (284.4 ± 115.9 ng/mL × 120 min) and PLA (20.2 ± 16.2 ng/mL × 120 min, p = 0.007) and between D100 and B500 (42.3 ± 17.6 ng/mL × 120 min, p = 0.04). Significant differences in D100 BBR AUC (284.4 ± 115.9 ng/mL×120 min) were found between PLA (20.2 ± 16.2 ng/mL × 120 min, p = 0.042) and B500 (42.3 ± 17.6 ng/mL × 120 min, p = 0.045). Berberine AUC values between D100 and D200 tended (p = 0.073) to be different. No significant differences in the levels of glucose (p = 0.97) and insulin (p = 0.24) were observed across the study protocol. These results provide preliminary evidence that four doses of a 100 mg dose of dihydroberberine and 200 mg dose of dihydroberberine produce significantly greater concentrations of plasma berberine across of two-hour measurement window when compared to a 500 mg dose of berberine or a placebo. The lack of observed changes in glucose and insulin were likely due to the short duration of supplementation and insulin responsive nature of study participants. Follow-up efficacy studies on glucose and insulin changes should be completed to assess the impact of berberine and dihydroberberine supplementation in overweight, glucose intolerant populations.

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Impact of Glucosamine Supplementation on Gut Health

Nutrients ◽

10.3390/nu13072180 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2180

Author(s):

Jessica M. Moon ◽

Peter Finnegan ◽

Richard A. Stecker ◽

Hanna Lee ◽

Kayla M. Ratliff ◽

...

Keyword(s):

Gastrointestinal Symptoms ◽

Short Chain Fatty Acids ◽

Fecal Microbiota ◽

Bowel Habit ◽

Total Amino Acid ◽

Crossover Fashion ◽

Gut Health ◽

Double Blind ◽

Branched Chain ◽

The Impact

Glucosamine (GLU) is a natural compound found in cartilage, and supplementation with glucosamine has been shown to improve joint heath and has been linked to reduced mortality rates. GLU is poorly absorbed and may exhibit functional properties in the gut. The purpose of this study was to examine the impact of glucosamine on gastrointestinal function as well as changes in fecal microbiota and metabolome. Healthy males (n = 6) and females (n = 5) (33.4 ± 7.7 years, 174.1 ± 12.0 cm, 76.5 ± 12.9 kg, 25.2 ± 3.1 kg/m2, n = 11) completed two supplementation protocols that each spanned three weeks separated by a washout period that lasted two weeks. In a randomized, double-blind, placebo-controlled, crossover fashion, participants ingested a daily dose of GLU hydrochloride (3000 mg GlucosaGreen®, TSI Group Ltd., USA) or maltodextrin placebo. Study participants completed bowel habit and gastrointestinal symptoms questionnaires in addition to providing a stool sample that was analyzed for fecal microbiota and metabolome at baseline and after the completion of each supplementation period. GLU significantly reduced stomach bloating and showed a trend towards reducing constipation and hard stools. Phylogenetic diversity (Faith’s PD) and proportions of Pseudomonadaceae, Peptococcaceae, and Bacillaceae were significantly reduced following GLU consumption. GLU supplementation significantly reduced individual, total branched-chain, and total amino acid excretion, with no glucosamine being detected in any of the fecal samples. GLU had no effect on fecal short-chain fatty acids levels. GLU supplementation provided functional gut health benefits and induced fecal microbiota and metabolome changes.

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Effect of Dehydroepiandrosterone Replacement on Lipoprotein Profile in Hypoadrenal Women

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-1774 ◽

2009 ◽

Vol 94 (3) ◽

pp. 761-764 ◽

Cited By ~ 21

Author(s):

Manivannan Srinivasan ◽

Brian A. Irving ◽

Ketan Dhatariya ◽

Katherine A. Klaus ◽

Stacy J. Hartman ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Lipoprotein Profile ◽

Double Blind ◽

Caucasian Women ◽

Study Participants ◽

The Impact ◽

To Receive

Abstract Context: Levels of dehydroepiandrosterone (DHEA) and its sulfate form (DHEAS) are inversely associated with cardiovascular mortality in men but not women. Very little evidence is available on the impact of DHEA administration on lipoprotein profile in women. DHEAS levels are very low/undetectable in hypoadrenal women. Objective: The objective of the study was to determine the impact of DHEA replacement on lipoprotein profile in hypoadrenal women. Design and Setting: A double-blind, randomized, placebo-controlled, cross-over design study was conducted at the Mayo Clinic. Participants: Thirty-three hypoadrenal Caucasian women (mean ± sd; age 50.3 ± 15.2 yr, body mass index 26.6 ± 4.4 kg/m2) took part in the study. Intervention: Study participants were assigned to receive either a placebo or 50 mg/d of DHEA for 3 months each. Lipid levels and lipoprotein profile were analyzed using the Lipo Science Lipoprotein nuclear magnetic resonance system. Main Outcome Measures: Changes in various lipoprotein sizes and levels were measured. Results: The DHEA period had higher plasma DHEAS levels than during placebo (<0.3 ± 0.0 vs. 3.5 ± 1.3 nmol/liter, P < 0.001). DHEA replacement significantly reduced total cholesterol (20.0 vs. −22, P = 0.02) and high-density lipoprotein (HDL) levels (2.0 vs. −6.0, P = 0.006) and tends to reduce triglyceride and total low-density lipoprotein levels. Although, DHEA replacement had no effect on low-density lipoprotein particle size, it significantly reduced larger HDL particles and to modest extent small HDL particles. Conclusions: Our study findings showed that oral DHEA administration in hypoadrenal women results in an unfavorable lipoprotein profile. The results warrant long-term studies to determine the impact of DHEA replacement on cardiovascular risk.

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Trans-Resveratrol Oral Bioavailability in Humans Using LipiSperse™ Dispersion Technology

Pharmaceutics ◽

10.3390/pharmaceutics12121190 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1190

Author(s):

David Briskey ◽

Amanda Rao

Keyword(s):

Single Dose ◽

Oral Bioavailability ◽

Maximum Concentration ◽

Randomized Study ◽

Venous Blood ◽

Area Under The Curve ◽

Fold Increase ◽

Double Blind ◽

Potential Health ◽

Liquid Chromatography Tandem Mass

Resveratrol is a naturally produced compound that has been well researched for its potential health benefits. The primary hindrance towards resveratrol’s therapeutic efficacy is its traditionally poor oral bioavailability. LipiSperse® is a novel delivery system designed to increase the dispersion of lipophilic ingredients, like resveratrol, in aqueous environments. This single-dose, double-blind, randomized study compared the pharmacokinetics of a commercially available resveratrol with (Veri-Sperse®) and without (Veri-te) the LipiSperse® delivery complex. Healthy adults randomly received a single dose of either 150 Veri-te, 75 Veri-Sperse®, or 150 mg Veri-Sperse®. Venous blood samples were taken prior to dosing in a fasted state and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 h post supplementation. Plasma trans-resveratrol conjugates were measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS). The area under the curve (AUC) (0–24 h), maximum concentration (Cmax), and time of maximum concentration (Tmax) of plasma conjugates were calculated. The 150 mg dose of Veri-Sperse® had a 2-fold increase in absorption (AUC) and a 3-fold increase in Cmax of trans-resveratrol conjugates compared to 150 mg Veri-te. There was no statistical difference between 75 Veri-Sperse and 150 mg Veri-te for AUC or Cmax of resveratrol conjugates. These findings provide support for the use of LipiSperse® to improve absorption of resveratrol.

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Study protocol for a double-blind randomised controlled trial investigating the impact of 12 weeks supplementation with aFucus vesiculosusextract on cholesterol levels in adults with elevated fasting LDL cholesterol who are overweight or have obesity

BMJ Open ◽

10.1136/bmjopen-2018-022195 ◽

2018 ◽

Vol 8 (12) ◽

pp. e022195 ◽

Cited By ~ 2

Author(s):

Margaret Murray ◽

Aimee L Dordevic ◽

Katherine H M Cox ◽

Andrew Scholey ◽

Lisa Ryan ◽

...

Keyword(s):

Risk Factors ◽

Disease Prevention ◽

Controlled Trial ◽

Venous Blood ◽

Brown Seaweed ◽

Density Lipoprotein ◽

Seaweed Extract ◽

Double Blind ◽

Markers Of Inflammation ◽

The Impact

IntroductionHyperlipidaemia, hyperglycaemia and chronic inflammation are risk factors for chronic diseases cardiovascular disease and type 2 diabetes. Polyphenols are bioactive compounds found in marine algae with potential antihyperlipidaemic, antihyperglycaemic and anti-inflammatory effects. The modulation of these risk factors using bioactive polyphenols may represent a useful strategy for disease prevention and management; research in humans, however, remains limited. This trial aims to determine the impact of a polyphenol-rich brown seaweed extract on fasting hyperlipidaemia, hyperglycaemia and inflammation. Effects on mood and cognition will also be evaluated.Methods and analysisFifty-eight hypercholesterolaemic participants who are overweight or have obesity will be randomised to receive either a polyphenol-rich brown seaweed extract (2000 mg dose containing 600 mg polyphenols) or placebo (2000 mg rice flour) daily for 12 weeks. Fasting venous blood samples will be taken at baseline, week 6 and week 12 of the intervention to assess serum cholesterol (total, low-density lipoprotein and high-density lipoprotein) and triglyceride concentrations, plasma glucose and insulin concentrations and markers of inflammation. Mood and cognitive function will be evaluated as exploratory outcomes. Independent t-tests or equivalent will be used to determine differences between the two groups in changes from baseline to week 12. Analysis of variance will be used to assess differences between the groups across the three time points (baseline, week 6 and week 12).Ethics and disseminationEthics approval has been granted by the Monash University Human Research Ethics Committee (2017-8689-10379). Results from this trial will be disseminated through publication in peer-reviewed journals, national and international presentations, and a PhD thesis. These results are essential to inform the use of polyphenol-rich brown seaweeds as a functional food or nutritional supplement ingredients for health promotion and disease prevention and management in humans.Trial registration numberACTRN12617001039370; Pre-results.

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CLRM-05. DRUG-RELEASING MICRODEVICES TO PREDICT RESPONSES TO TARGETED THERAPIES IN PATIENTS WITH GLIOMAS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab112.004 ◽

2021 ◽

Vol 3 (Supplement_4) ◽

pp. iv2-iv2

Author(s):

Sarah Blitz ◽

Christine Dominas ◽

Michael J Pannell ◽

E Antonio Chiocca ◽

Patrick Y Wen ◽

...

Keyword(s):

Targeted Therapies ◽

Tumor Tissue ◽

Pilot Trial ◽

Preliminary Evidence ◽

Surrounding Tissue ◽

Patient Specific ◽

Molecular Response ◽

Molecular Features ◽

Multiple Drugs ◽

The Impact

Abstract Genomic studies of tumor specimens are becoming standard of care in patients with gliomas to characterize druggable molecular features. Unfortunately, with the exception of IDH1-R132 mutation and MGMT promoter methylation, molecular markers have failed to predict clinical responses to drugs, and the impact of targeted therapies remains minimal. There is a need for a high-throughput, patient-specific, and significantly predictive method to inform a most effective personalized therapy. This pilot trial tests the safety and feasibility of drug-releasing microdevices which are temporarily implanted into the tumor during a standard craniotomy. They release microdoses of up to 20 drugs or drug combinations into surrounding tissue in a controlled spatial distribution. The devices, together with a cuff of surrounding tumor tissue, are removed at the end of surgery, and the tissue is analyzed for biological and molecular response markers allowing for in situ characterization of the drug efficacy. Four patients have been enrolled to date, out of a total planned of six. Two microdevices were implanted into each tumor (8 total devices). Average indwelling time in tumor tissue was 139 minutes. Eight devices (100%) were successfully retrieved, and all surgeries were completed without immediate (<24 hours) or delayed (<30 days) complications. Seven (87%) specimens were of adequate quality, allowing for planned histological and molecular studies. For all analyzed specimens, the intraoperative incubation time was sufficient to observe: 1) Drug concentration gradients; 2) Differential molecular signs of cell toxicity (DNA damage and Caspase 3 activation); 3) Whole genome transcriptional changes; 4) Tumor microenvironment composition; and 5) Preliminary evidence of concordance between the biological readout obtained from microdevice analysis and clinical response. Drug-releasing microdevices were well tolerated, seamlessly integrated in standard craniotomy workflow, and allowed for collection of a significant amount of data related to the differential efficacy of multiple drugs in a personalized manner.

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Acute effects of protein composition and fibre enrichment of yogurt consumed as snacks on appetite sensations and subsequent ad libitum energy intake in healthy men

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2014-0403 ◽

2015 ◽

Vol 40 (10) ◽

pp. 980-989 ◽

Cited By ~ 10

Author(s):

Caroline Y. Doyon ◽

Angelo Tremblay ◽

Laurie-Eve Rioux ◽

Caroline Rhéaume ◽

Katherine Cianflone ◽

...

Keyword(s):

Energy Intake ◽

Area Under The Curve ◽

Protein Composition ◽

Double Blind ◽

Protein Ratio ◽

Healthy Men ◽

Visual Analog Scales ◽

Significant Difference ◽

Ad Libitum ◽

The Impact

The objective of the study was to assess the impact of protein composition and/or fibre enrichment of yogurt on appetite sensations and subsequent energy intake. In this double-blind crossover study, 20 healthy men (aged 32.4 ± 9.1 years) were submitted to 5 randomized testing sessions, during which they had to consume 5 isocaloric and isonproteinemic yogurt snacks (120-g servings, ∼230 kJ, ∼4.5 g protein) differing by their casein-to-whey protein ratio (C:W) or dietary fibre content: (i) control C:W = 2.8:1; (ii) high whey (HW) C:W = 1.5:1, and fibre-enriched formulations using control; (iii) 2.4 g of inulin; (iv) 1.9 g of inulin and 0.5 g of β-glucan (+IN-βG); and (v) 0.5 g of β-glucan. Appetite sensations were assessed using 150-mm visual analog scales. Plasma variables (glucose, insulin, ghrelin) were measured at 30-min intervals post-yogurt consumption for 2 h. Finally, energy intakes during ad libitum lunches offered 2 h after yogurt snacks were recorded. None of the yogurts impacted appetite sensations. Ad libitum energy intake was significantly different only between HW and control yogurts (–812 kJ; p = 0.03). Regarding post-yogurt plasma variables, a significant difference was found only between ghrelin area under the curve of the +IN-βG and the HW yogurts (–15 510 pmol/L per 120 min, p = 0.04). In conclusion, although appetite sensations were not influenced by variations in yogurts’ protein compositions, a reduced energy intake was observed during the ad libitum lunch after the HW yogurt that may be attributable to its lower C:W. Surprisingly, the fibre enrichments studied did not exert effect on appetite sensations and energy intake.

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Tissue Factor-Exposing Microparticles at the Site of Hemostasis Activation.

Blood ◽

10.1182/blood.v106.11.3944.3944 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3944-3944 ◽

Cited By ~ 1

Author(s):

Verena Gartner ◽

Barbara Lubscyk ◽

Marietta Kollars ◽

Paul A. Kyrle ◽

Ansgar Weltermann

Keyword(s):

Tissue Factor ◽

Venous Blood ◽

Annexin V ◽

Skin Incision ◽

Double Blind ◽

Shed Blood ◽

Activated State ◽

The Impact

Abstract Introduction: Tissue factor exposing microparticles (TF+ MPs) are capable to activate hemostasis in vitro. The aim of this study was to investigate the impact of TF+ MPs during physiologic activation of hemostasis in vivo in human. Methods: In a double-blind, cross-over study healthy male volunteers (n=13) were randomized to 7 days treatment with 100 mg aspirin and placebo, respectively. At the end of each treatment period TF+ MPs were determined in venous blood and in blood emerging from a skin incision reflecting hemostasis in an activated state (shed blood). TF+ MPs were analyzed by flow cytometry after staining with annexin V, a TF-antibody and cell-specific antibodies. Results: Compared to venous blood, the median (interquartile range) number of TF+ MPs was significantly higher in shed blood: 16.2 (11.3 – 20.1) k/ml vs. 8.2 (5.9 – 14.8) k/ml (p = 0.004). TF+ MPs from platelets were higher in shed blood than in venous blood [4.7 (3.7 – 8.6) k/ml vs. 3.3 (2.0 – 5.0) k/ml, p = 0.03], whereas TF+ MPs from endothelial cells were not [1.7 (1.2 – 5.8) k/ml vs. 2.7 (1.7 – 4.5) k/ml, p = 0.9]. Aspirin did not significantly influence the level of TF-MPs both in venous blood and in shed blood. Conclusion: High levels of TF+ MPs can be detected at the site of physiologic activation of hemostasis in vivo in human.

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4402 The effects of hemodilution in vitro on coagulation in term parturients using thromboelastometry

Journal of Clinical and Translational Science ◽

10.1017/cts.2020.434 ◽

2020 ◽

Vol 4 (s1) ◽

pp. 147-147

Author(s):

Chloe Getrajdman ◽

Matthew Sison ◽

Hung-Mo Lin ◽

Daniel Katz

Keyword(s):

Blood Coagulation ◽

Conflicts Of Interest ◽

Venous Blood ◽

Area Under The Curve ◽

Rotational Thromboelastometry ◽

Significant Difference ◽

History Of ◽

The Impact

OBJECTIVES/GOALS: Little is known about the effect of hemodilution with crystalloid on blood coagulation in obstetric patients. The purpose of our study was to examine the impact of hemodilution on components of blood coagulation using rotational thromboelastometry (ROTEM®) in term parturients METHODS/STUDY POPULATION: This is a prospective, observational pilot study including 35 healthy, pregnant patients at term (≥37 weeks) without history of bleeding or clotting disorder or on medication affecting coagulation. Venous blood samples were collected from all patients and divided into specimen tubes to generate varying degrees of hemodilution with Plasma-Lyte (0%, 20%, 25%, 30%, 35%, 40%, 45%, 55%, 60%, 65%, 70%, 75%, 80%). Rotational thromboelastometry was then performed on samples to assess for coagulation changes. RESULTS/ANTICIPATED RESULTS: EXTEM (extrinsically activated assay) clotting time (CT) became prolonged at 65% hemodilution and above, and the median CT was in the coagulopathic range (>80 seconds) at a dilution of 80%. FIBTEM (extrinsically activated assay with platelet inhibitor, primarily measuring contribution of fibrinogen to coagulation) amplitude at 5 minutes (A5) began to diminish at 35% hemodilution, with the median A5 in the coagulopathic range (<12 mm) at 55% hemodilution. The area under the curve (AUC), a marker of clot strength, for EXTEM and FIBTEM consistently declined as hemodilution increased. Greater decreases in FIBTEM AUC were seen compared to EXTEM AUC, with the ratio of FIBTEM:EXTEM AUC at each dilution demonstrating a statistically significant difference from baseline. DISCUSSION/SIGNIFICANCE OF IMPACT: All thromboelastometry values demonstrated a hypocoagulable trend as hemodilution increased. However, the samples analyzed by the FIBTEM assay trended toward a coagulopathy at a lower degree of hemodilution compared to the EXTEM assay. As FIBTEM tests analyze the role of fibrinogen in hemostasis and EXTEM tests analyze the role of platelets, our findings suggest that platelets may be able to withstand higher degrees of hemodilution before impairing hemostasis compared to fibrinogen. These findings support the growing body of literature that in early stages of severe obstetric hemorrhage, the prioritization of fibrinogen replacement may be critical in preventing further coagulopathy. CONFLICT OF INTEREST DESCRIPTION: All authors have no conflicts of interest to report.

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A-192 Preliminary Evidence to Support Use of Personal Protective Equipment (PPE) during Administration of the Neuropsychological Assessment Battery (NAB)

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acab062.210 ◽

2021 ◽

Vol 36 (6) ◽

pp. 1247-1247

Author(s):

Sierra Iwanicki ◽

David M Lechuga ◽

Lisa Fasnacht-Hill

Keyword(s):

Neuropsychological Assessment ◽

Personal Protective Equipment ◽

Standardized Test ◽

American Psychological Association ◽

Preliminary Evidence ◽

Protective Equipment ◽

Test Administration ◽

Assessment Battery ◽

Neuropsychological Assessment Battery ◽

The Impact

Abstract Objective In June 2020, the American Psychological Association acknowledged that use of personal protective equipment (PPE) was key to psychologists safely resuming in-person services. However, there is no empirical evidence on the impact of PPE in delivering the provision of essential mental health services. Of particular concern is the unprecedented use of PPE during psychological assessment, which inherently breaches standardized test administration procedures. The current study provides preliminary evidence to support use of PPE during administration of the Neuropsychological Assessment Battery (NAB). Method This is a paired-case control study in which participants were administered the NAB using PPE. These individuals were matched based on age, sex, and education with participants from the same setting who were administered the NAB using standardized test administration procedures. Results Independent samples t-tests were run to determine if there were differences in index scores between the PPE and non-PPE groups. There were no significant differences in the standard scores for the NAB Total Index and all NAB Index scores with the exception of Language. Among the subtests that comprise the Language Index, only T-scores on the Oral Production subtest difference significantly between the PPE and non-PPE groups. Conclusions With the exception of the Language Index, index standard scores for both groups were found to be generally statistically equivalent. Given the sample size and setting limitations, no clear conclusions can be drawn about why performance varied between groups on the Language Index. Nevertheless, these data provide preliminary support for the use of PPE during administration of selected modules of the NAB.

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The impact of participant engagement activities in supporting dapivirine ring use among participants enrolled in the Phase III MTN-020/ASPIRE study

10.21203/rs.3.rs-235289/v1 ◽

2021 ◽

Author(s):

Morgan Garcia ◽

Ellen Luecke ◽

Ashley Mayo ◽

Rachel Scheckter ◽

Patrick Ndase ◽

...

Keyword(s):

Study Participant ◽

Sub Saharan Africa ◽

Phase Iii ◽

Controlled Study ◽

Double Blind ◽

Participant Engagement ◽

Income Status ◽

Adherence Support ◽

Study Participants ◽

The Impact

Abstract Background: Low adherence to investigational products can negatively impact study outcomes, limiting the ability to demonstrate efficacy. To continue advancing potential new HIV prevention technologies for at-risk individuals, efforts are needed to improve adherence among study participants. In MTN-020/ASPIRE, a phase III randomized, double-blind, placebo-controlled study of the dapivirine vaginal ring carried out across 15 sites in sub-Saharan Africa, a multifaceted approach to adherence support was implemented, including a strong focus on participant engagement activities (PEAs). In this manuscript, we describe PEAs and participant attendance, and analyze the potential impact of PEAs on ring use. Methods: All sites implemented PEAs and submitted activity and attendance reports to the study management team throughout the study. Participant demographics were collected via case report forms. Ring use was estimated based on residual dapivirine remaining in the last returned ring by each participant and connected to PEA attendance using participant identification numbers. We used multivariate logistic regression to explore differences in ring use between PEA attendance groups and reviewed qualitative reports for illustrative quotes highlighting participant experiences with PEAs. Results: 2,312 of 2,629 study participants attended at least one of 389 PEAs conducted across sites. Participant country and partner knowledge of study participation were most strongly associated with PEA attendance (p < 0.005) with age, education, and income status also associated with event attendance (p < 0.05). When controlling for these variables, participants who attended at least one event were more likely to return a last ring showing at least some use (AOR=3.52) than those who never attended an event. There was an even stronger correlation between a last returned ring showing use and participant attendance at multiple events (AOR=4.03). Conclusions: Our analysis supports the growing body of work illustrating the importance of meaningfully engaging research participants to achieve study success and aligns with other analyses of adherence support efforts during ASPIRE. While causation between PEA attendance and product use cannot be established, residual drug levels in returned rings strongly correlated with participant attendance at PEAs, and the benefits of incorporating PEAs should be considered when designing future studies of investigational products.

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