Changes In Actual And Perceived Physical Abilities In Clinically Obese Children: A 9-Month Multi-Component Intervention Study

Objectives

(1) To examine relationships among changes in physical activity, physical fitness and some psychosocial determinants of activity behavior in a clinical sample of obese children involved in a multi-component program; (2) to investigate the causal relationship over time between physical activity and one of its strongest correlates (i.e. perceived physical ability).

Methods

Self-reported physical activity and health-related fitness tests were administered before and after a 9-month intervention in 24 boys and 20 girls aged 8 to 11 years. Individuals’ perceptions of strength, speed and agility were assessed using the Perceived Physical Ability Scale, while body image was measured using Collins’ Child Figure Drawings.

Results

Findings showed that body mass index, physical activity, performances on throwing and weight-bearing tasks, perceived physical ability and body image significantly improved after treatment among obese children. Gender differences were found in the correlational analyses, showing a link between actual and perceived physical abilities in boys, but not in girls. For the specific measurement interval of this study, perception of physical ability was an antecedent and not a potential consequence of physical activity.

Conclusions

Results indicate that a multi-component activity program not based merely on a dose-effect approach enhances adherence of the participants and has the potential to increase the lifelong exercise skills of obese children. Rather than focusing entirely on diet and weight loss, findings support the inclusion of interventions directed toward improving perceived physical ability that is predictive of subsequent physical activity.     

Effectiveness of a Multi-Component Intervention for Overweight and Obese Children (Nereu Program): A Randomized Controlled Trial

Introduction

Treatment of childhood obesity is a complex challenge for primary health care professionals.

Objectives

To evaluate the effectiveness of the Nereu Program in improving anthropometric parameters, physical activity and sedentary behaviours, and dietary intake.

Methods

Randomized, controlled, multicentre clinical trial comparing Nereu Program and usual counselling group interventions in primary care settings. The 8-month study recruited 113 children aged 6 to 12 years with overweight/obesity. Before recruitment, eligible participants were randomly allocated to an intensive, family-based multi-component behavioural intervention (Nereu Program group) or usual advice from their paediatrician on healthy eating and physical activity. Anthropometric parameters, objectively measured sedentary and physical activity behaviours, and dietary intake were evaluated pre- and post-intervention.

Results

At the end of the study period, both groups achieved a similar decrease in body mass index (BMIsd) compared to baseline. Nereu Program participants (n = 54) showed greater increases in moderate-intense physical activity (+6.27% vs. -0.61%, p<0.001) and daily fruit servings (+0.62 vs. +0.13, p<0.026), and decreased daily soft drinks consumption (-0.26 vs. -0.02, p<0.047), respectively, compared to the counselling group (n = 59).

Conclusions

At the end of the 8-month intervention, participants in the Nereu Program group showed improvement in physical activity and dietary behaviours, compared to the counselling group.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01878994","term_id":"NCT01878994"}}NCT01878994     

An Adaptive Physical Activity Intervention for Overweight Adults: A Randomized Controlled Trial

Background

Physical activity (PA) interventions typically include components or doses that are static across participants. Adaptive interventions are dynamic; components or doses change in response to short-term variations in participant''s performance. Emerging theory and technologies make adaptive goal setting and feedback interventions feasible.

Objective

To test an adaptive intervention for PA based on Operant and Behavior Economic principles and a percentile-based algorithm. The adaptive intervention was hypothesized to result in greater increases in steps per day than the static intervention.

Methods

Participants (N = 20) were randomized to one of two 6-month treatments: 1) static intervention (SI) or 2) adaptive intervention (AI). Inactive overweight adults (85% women, M = 36.9±9.2 years, 35% non-white) in both groups received a pedometer, email and text message communication, brief health information, and biweekly motivational prompts. The AI group received daily step goals that adjusted up and down based on the percentile-rank algorithm and micro-incentives for goal attainment. This algorithm adjusted goals based on a moving window; an approach that responded to each individual''s performance and ensured goals were always challenging but within participants'' abilities. The SI group received a static 10,000 steps/day goal with incentives linked to uploading the pedometer''s data.

Results

A random-effects repeated-measures model accounted for 180 repeated measures and autocorrelation. After adjusting for covariates, the treatment phase showed greater steps/day relative to the baseline phase (p<.001) and a group by study phase interaction was observed (p = .017). The SI group increased by 1,598 steps/day on average between baseline and treatment while the AI group increased by 2,728 steps/day on average between baseline and treatment; a significant between-group difference of 1,130 steps/day (Cohen''s d = .74).

Conclusions

The adaptive intervention outperformed the static intervention for increasing PA. The adaptive goal and feedback algorithm is a “behavior change technology” that could be incorporated into mHealth technologies and scaled to reach large populations.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01793064","term_id":"NCT01793064"}}NCT01793064     

Lifestyle Intervention Using an Internet-Based Curriculum with Cell Phone Reminders for Obese Chinese Teens: A Randomized Controlled Study

ObjectivesObesity is an increasing public health problem affecting young people. The causes of obesity are multi-factorial among Chinese youth including lack of physical activity and poor eating habits. The use of an internet curriculum and cell phone reminders and texting may be an innovative means of increasing follow up and compliance with obese teens. The objectives of this study were to determine the feasibility of using an adapted internet curriculum and existing nutritional program along with cell phone follow up for obese Chinese teens.ResultsThe use of the internet-based curriculum was shown to be feasible as evidenced by the high recruitment rate, internet log-in rate, compliance with completing the curriculum and responses to phone reminders. No significant differences in weight were found between IT, sLMP and control groups.ConclusionAn internet-based curriculum with cell phone reminders as a supplement to usual care of obesity is feasible. Further study is required to determine whether an internet plus text intervention can be both an effective and a cost-effective adjunct to changing weight in obese youth.

Trial Registration

Chinese Clinical Trial Registry ChiCTR-TRC-12002624     

A Pilot Randomized Controlled Trial of a Clinic and Home‐Based Behavioral Intervention to Decrease Obesity in Preschoolers

We evaluated the efficacy of a 6‐month clinic and home‐based behavioral intervention (Learning about Activity and Understanding Nutrition for Child Health; LAUNCH) to reduce obesity in preschool children ≥95th BMI percentile compared to enhanced standard of care (Pediatrician Counseling; PC). LAUNCH was a family‐based behavioral intervention that taught parents to use child behavior management strategies to increase healthy eating and activity for their children and themselves. PC presented the same diet and activity recommendations, but was delivered in a one‐time PC session. Eighteen children aged 2–5 years (mean 4.71 ± 1.01) with an average BMI percentile of 98 (±1.60) and an overweight parent were randomized to LAUNCH or PC. Assessments were conducted at baseline, 6 months (end of LAUNCH treatment) and 12 months (6 months following LAUNCH treatment). LAUNCH showed a significantly greater decrease on the primary outcomes of child at month 6 (post‐treatment) BMI z (?0.59 ± 0.17), BMI percentile (?2.4 ± 1.0), and weight gain (?2.7 kg ± 1.2) than PC and this difference was maintained at follow‐up (month 12). LAUNCH parents also had a significantly greater weight loss (?5.5 kg ± 0.9) at month 6 and 12 (?8.0 kg ± 3.5) than PC parents. Based on the data from this small sample, an intensive intervention that includes child behavior management strategies to improve healthy eating and activity appears more promising in reducing preschool obesity than a low intensity intervention that is typical of treatment that could be delivered in primary care.     

Circulating Endothelial Progenitor Cells in Castration Resistant Prostate Cancer: A Randomized,Controlled, Biomarker Study

Background

Endothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC) patients.

Patients and methods

Chemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d), in combination with docetaxel (75 mg/m²) or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy.

Results

A total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable) counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001). However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30%) patients responded to therapy with a 50% PSA decline, while 9 (64%) patients showed a PSA decline in the combination group (n.s.). The median PFS in the docetaxel monotherapy group was 3.1 months (2.6–3.6 months, 95% CI) and 6.2 months (4.9–7.4 months, 95% CI; p = 0.062) in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable.

Conclusion

In summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However, docetaxel/sunitinib therapy resulted in a better response in terms of PSA decline and a trend towards improved PFS.

Trial Registery

clinicaltrialsregister.eu EudraCT 2007-003705-27     

A Primary Care Intervention for Weight Loss: Results of a Randomized Controlled Pilot Study

Most primary care providers (PCPs), constrained by time and resources, cannot provide intensive behavioral counseling for obesity. This study evaluated the effect of using medical assistants (MAs) as weight loss counselors. The study was a randomized controlled trial conducted in two primary care offices at an academic medical center. Patients (n = 50) had a BMI of 27–50 kg/m² and no contraindications to weight loss. They were randomized to quarterly PCP visits and weight loss materials (Control group) or to the same approach combined with eight visits with a MA over 6 months (Brief Counseling). Outcomes included change in weight and cardiovascular risk factors (glucose, lipids, blood pressure, and waist circumference). Patients in the Brief Counseling and Control groups lost 4.4 ± 0.6 kg (5.1 ± 0.7% of initial weight) and 0.9 ± 0.6 kg (1.0 ± 0.7%), respectively, at month 6 (P < 0.001). There were no significant differences between groups for changes in cardiovascular risk factors. Brief Counseling patients regained weight between month 6 and month 12, when MA visits were discontinued. Attrition was 10% after 6 months and 6% after 12 months. Brief Counseling by MAs induced significant weight loss during 6 months. Office‐based obesity treatment should be tested in larger trials and should include weight loss maintenance counseling.     

Web‐based Weight Loss in Primary Care: A Randomized Controlled Trial

Evidence is lacking regarding effective and sustainable weight loss approaches for use in the primary care setting. We conducted a 12-week randomized controlled trial to evaluate the short-term efficacy of a web-based weight loss intervention among 101 primary care patients with obesity and hypertension. Patients had access to a comprehensive website that used a moderate-intensity weight loss approach designed specifically for web-based implementation. Patients also participated in four (two in-person and two telephonic) counseling sessions with a health coach. Intent-to-treat analysis showed greater weight loss at 3 months (−2.56 kg; 95% CI −3.60, −1.53) among intervention participants (−2.28 ± 3.21 kg), relative to usual care (0.28 ± 1.87 kg). Similar findings were observed among intervention completers (−3.05 kg; 95% CI −4.24, −1.85). High rates of participant retention (84%) and website utilization were observed, with the greatest weight loss found among those with a high frequency of website logins (quartile 4 vs. 1: −4.16 kg; 95% CI −1.47, −6.84). The intervention's approach promoted moderate weight loss at 12 weeks, though greater weight loss was observed among those with higher levels of website utilization. Efficacious web-based weight loss interventions can be successfully offered in the primary care setting.     

Content-Specificity in Verbal Recall: A Randomized Controlled Study

In this controlled experiment we examined whether there are content effects in verbal short-term memory and working memory for verbal stimuli. Thirty-seven participants completed forward and backward digit and letter recall tasks, which were constructed to control for distance effects between stimuli. A maximum-likelihood mixed-effects logistic regression revealed main effects of direction of recall (forward vs backward) and content (digits vs letters). There was an interaction between type of recall and content, in which the recall of digits was superior to the recall of letters in verbal short-term memory but not in verbal working memory. These results demonstrate that the recall of information from verbal short-term memory is content-specific, whilst the recall of information from verbal working memory is content-general.     

Adipocytes IGFBP‐2 Expression in Prepubertal Obese Children

Aims of the study were to measure insulin‐like growth factor‐binding protein‐2 (IGFBP‐2) expression by abdominal subcutaneous adipocytes and to assess the relationship between IGFBP‐2 expression, circulating IGFBP‐2, obesity, and insulin sensitivity in obese children. Thirty‐eight obese children were recruited. Insulin sensitivity was assessed by intravenous glucose tolerance test and body composition by total‐body dual‐energy X‐ray absorptiometry. Serum free and total IGF‐I, IGFBP‐2, adiponectin, and leptin were measured. Relative quantification of IGFBP‐2 mRNA by subcutaneous adipose tissue biopsies was obtained using real‐time PCR. Circulating IGFBP‐2 was positively associated with insulin sensitivity, in agreement with previous studies. IGFBP‐2 expression was associated with fat mass percentage (r = 0.656; P < 0.02), insulin sensitivity (r = ?0.604; P < 0.05), free IGF‐I (r = 0.646; P < 0.05), and leptin (r = 0.603; P < 0.05), but not with circulating IGFBP‐2 (r = 0.003, P = ns). The association between IGFBP‐2 expression and adiposity (r = 0.648; P < 0.05) was independent of insulin sensitivity (covariate). In conclusion, circulating IGFBP‐2 was positively associated with insulin sensitivity. IGFBP‐2 was expressed by subcutaneous abdominal adipocytes of obese children and increased with adiposity, independently from the level of insulin sensitivity. IGFBP‐2 expression may potentially be one of the local mechanisms used by adipocytes to limit further fat gain.     

Circulating Irisin Levels Are Not Affected by Coffee Intake: A Randomized Controlled Trial

Irisin, secreted by skeletal muscle and possibly fat, is hypothesized to play an important role in modulating energy expenditure, obesity and metabolism. Coffee consumption also increases energy expenditure and leads to positive metabolic effects, but whether these effects are mediated by irisin remains unknown. The objective of this study was to determine the association between baseline irisin levels and the metabolic profile in humans and to investigate whether consumption of caffeinated coffee alters irisin levels. To this end, a secondary analysis was performed investigating irisin levels at baseline and after eight weeks in 32 healthy, overweight coffee drinkers who were randomized to consumption of 5 cups per day of instant caffeinated coffee, decaffeinated coffee, or water. Spearman correlation and analysis of covariance analyses were performed to identify possible associations. Irisin levels were positively correlated with waist circumference (r = 0.41, p = 0.02), fat mass (r = 0.44, p = 0.01) and CRP (r = 0.47, p = 0.007). Though there was a trend towards increased levels of irisin over time in the caffeinated coffee group (+1.8%) when compared to the placebo group (−4%) this did not reach statistical significance (p = 0.75 for the trend). This first randomized trial failed to reveal any effects of coffee consumption on irisin levels, but a larger trial, appropriately sized on the basis of data provided by this study, is needed to conclusively investigate such a relationship.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00305097","term_id":"NCT00305097"}}NCT00305097     

A Pilot Internet‐Based Behavioral Weight Loss Intervention with or without Commercially Available Portion‐Controlled Foods

Objective : To evaluate the short‐term impact of portion‐controlled food provision in combination with an Internet behavioral weight loss program on weight, blood cholesterol, and blood glucose levels. Design and Methods : Fifty participants, mean age 46 ± 10.7 years and mean body mass index 35.1 ± 3.8 kg/m², were randomized to one of two study groups, an Internet behavioral weight loss program (Internet‐alone; n = 25) or an Internet behavioral weight loss program plus a commercially available portion‐controlled diet (Internet + PCD; n = 25) for 12 weeks. Results : An intent‐to‐treat analysis found that the mean weight change in the Internet + PCD group was ?5.7 ± 5.6 kg and in the Internet‐alone group (n = 25) was ?4.1 ± 4.0 kg (P = 0.26). Participants in the Internet + PCD group achieved significantly greater improvements in blood glucose (?2.6 ± 5.7 vs. 1.4 ± 11.0 mg/dl; P = 0.05) and LDL cholesterol (?8.2 ± 18.0 vs. ?0.6 ± 21.0 mg/dl; P = 0.04), compared with Internet‐alone group. Conclusions : These data suggest that there may be short‐term clinical benefit in using a PCD in conjunction with a behavioral Internet‐based weight loss program to enhance weight loss and improve health indicators.     

Changes in Physical Activity over Time in Young Children: A Longitudinal Study Using Accelerometers

Previous research has suggested that marked declines in physical activity occur during the preschool years, and across the transition into school. However, longitudinal studies using objective measures of activity have been limited by sample size and length of follow-up. The aims of this study were to determine how overall activity and time in different intensities of activity change in children followed from 3 to 7 years. Children (n = 242) wore Actical accelerometers at 3, 4, 5, 5.5, 6.5 and 7 years of age during all waking and sleeping hours for a minimum of 5 days. Time in sedentary (S), light (L), moderate (M), and vigorous (V) physical activity was determined using available cut points. Data were analyzed using a mixed model and expressed as counts per minute (cpm, overall activity) and the ratio of active time to sedentary time (LMV:S), adjusted for multiple confounders including sex, age, time worn, and weather. At 5 years, physical activity had declined substantially to around half that observed at 3 years. Although starting school was associated with a further short-term (6-month) decline in activity (cpm) in both boys (difference; 95% CI: -98; -149, -46) and girls (-124; -174, -74, both P<0.001), this proved to be relatively transient; activity levels were similar at 6-7 years as they were just prior to starting school. Boys were more physically active than girls as indicated by an overall 12% (95% CI: 2, 22%) higher ratio of active to sedentary time (P = 0.014), but the pattern of this difference did not change from 3 to 7 years. Time worn and weather variables were significant predictors of activity. In conclusion, both boys and girls show a marked decline in activity from 3 to 4 years of age, a decrease that is essentially maintained through to 7 years of age. Factors driving this marked decrease need to be determined to enable the development of targeted interventions.     

Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial

Background

Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%).

Methods and Findings

This randomized controlled trial included children (0.5–10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan–Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7g/dl 7 d or more after admission.The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI −7, 5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI −12, 1; p = 0.24). Delayed parasite clearance was associated with the ^N86YPfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms.A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner.

Conclusions

A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children.

Trial registration

Pan African Clinical Trials Registry PACTR201102000277177     

Cost-Effectiveness of a Community Pharmacist Intervention in Patients with Depression: A Randomized Controlled Trial (PRODEFAR Study)

Background

Non-adherence to antidepressants generates higher costs for the treatment of depression. Little is known about the cost-effectiveness of pharmacist''s interventions aimed at improving adherence to antidepressants. The study aimed to evaluate the cost-effectiveness of a community pharmacist intervention in comparison with usual care in depressed patients initiating treatment with antidepressants in primary care.

Methods

Patients were recruited by general practitioners and randomized to community pharmacist intervention (87) that received an educational intervention and usual care (92). Adherence to antidepressants, clinical symptoms, Quality-Adjusted Life-Years (QALYs), use of healthcare services and productivity losses were measured at baseline, 3 and 6 months.

Results

There were no significant differences between groups in costs or effects. From a societal perspective, the incremental cost-effectiveness ratio (ICER) for the community pharmacist intervention compared with usual care was €1,866 for extra adherent patient and €9,872 per extra QALY. In terms of remission of depressive symptoms, the usual care dominated the community pharmacist intervention. If willingness to pay (WTP) is €30,000 per extra adherent patient, remission of symptoms or QALYs, the probability of the community pharmacist intervention being cost-effective was 0.71, 0.46 and 0.75, respectively (societal perspective). From a healthcare perspective, the probability of the community pharmacist intervention being cost-effective in terms of adherence, QALYs and remission was of 0.71, 0.76 and 0.46, respectively, if WTP is €30,000.

Conclusion

A brief community pharmacist intervention addressed to depressed patients initiating antidepressant treatment showed a probability of being cost-effective of 0.71 and 0.75 in terms of improvement of adherence and QALYs, respectively, when compared to usual care. Regular implementation of the community pharmacist intervention is not recommended.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00794196","term_id":"NCT00794196"}}NCT00794196     

Therapeutic Intervention in Multiple Sclerosis with Alpha B-Crystallin: A Randomized Controlled Phase IIa Trial

As a molecular chaperone and activator of Toll-like receptor 2-mediated protective responses by microglia and macrophages, the small heat shock protein alpha B-crystallin (HspB5) exerts therapeutic effects in different animal models for neuroinflammation, including the model for multiple sclerosis (MS). Yet, HspB5 can also stimulate human antigen-specific memory T cells to release IFN-γ, a cytokine with well-documented detrimental effects during MS. In this study, we explored in a Phase IIa randomized clinical trial the therapeutic application of HspB5 in relapsing-remitting MS (RR-MS), using intravenous doses sufficient to support its protective effects, but too low to trigger pathogenic memory T-cell responses. These sub-immunogenic doses were selected based on in vitro analysis of the dose-response profile of human T cells and macrophages to HspB5, and on the immunological effects of HspB5 in healthy humans as established in a preparatory Phase I study. In a 48-week randomized, placebo-controlled, double-blind Phase IIa trial, three bimonthly intravenous injections of 7.5, 12.5 or 17.5 mg HspB5 were found to be safe and well tolerated in RR-MS patients. While predefined clinical endpoints did not differ significantly between the relatively small groups of MS patients treated with either HspB5 or placebo, repeated administration especially of the lower doses of HspB5 led to a progressive decline in MS lesion activity as monitored by magnetic resonance imaging (MRI), which was not seen in the placebo group. Exploratory linear regression analysis revealed this decline to be significant in the combined group receiving either of the two lower doses, and to result in a 76% reduction in both number and total volumes of active MRI lesions at 9 months into the study. These data provide the first indication for clinical benefit resulting from intervention in RR-MS with HspB5. Trial Registration: ClinicalTrials.gov Phase I: NCT02442557; Phase IIa: NCT02442570