The Arthritis,Diet and Activity Promotion Trial (ADAPT): design,rationale, and baseline results

Osteoarthritis (OA) of the knee leads to restrictions of physical activity and ability to perform activities of daily living. Obesity is a risk factor for knee OA and it appears to exacerbate knee pain and disability. The Arthritis, Diet, and Activity Promotion Trial (ADAPT) was developed to test the efficacy of lifestyle behavioral changes on physical function, pain, and disability in obese, sedentary older adults with knee OA. This controlled trial randomized 316 sedentary overweight and obese older adults in a two-by-two factorial design into one of four 18-month duration intervention groups: Healthy Lifestyle Control; Dietary Weight Loss; Structured Exercise; or Combined Exercise and Dietary Weight Loss. The weight-loss goal for the diet groups was a 5% loss at 18 months. The intervention was modeled from principles derived from the group dynamics literature and social cognitive theory. Exercise training consisted of aerobic and strength training for 60 minutes, three times per week in a group and home-based setting. The primary outcome measure was self-report of physical function using the Western Ontario and McMaster University Osteoarthritis Index. Other measurements included timed stair climb, distance walked in 6 minutes, strength, gait, knee pain, health-related quality of life, knee radiographs, body weight, dietary intake, and cost-effectiveness of the interventions. We report baseline data stratified by level of overweight and obesity focusing on self-reported physical function and physical performance tasks. The results from ADAPT will provide approaches clinicians should recommend for behavioral therapies that effectively reduce the incidence of disability associated with knee OA.     

The Lipoprotein and Coronary Atherosclerosis Study (LCAS): Design,methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia

Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease (CHD) and normal or only slightly elevated plasma cholesterol concentrations. The one published angiographic trial designed to examine this question found no benefit. Additional prospective data will be provided by the Lipoprotein and Coronary Atherosclerosis Study (LCAS), a randomized, double-blind, placebo-controlled trial of fluvastatin therapy (20 mg twice daily) monitored by both quantitative coronary angiography (QCA) and, in a subset of patients, positron-emission tomography (PET). Eligible subjects in LCAS were men and women 35–75 years of age with low-density lipoprotein (LDL) cholesterol of 115–190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30–75% diameter stenosis. Among the 429 patients randomized (mean age 58.8, 81% male), mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prerandomization LDL cholesterol of 160 mg/dL or higher also received open-label adjunctive cholestyramine. The primary endpoint is within-patient per-lesion change in minimum lumen diameter (MLD) as measured by QCA at baseline and 2.5-year follow-up. All evaluable lesions had MLD at least 0.8 mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25% of the reference lumen diameter at baseline. Data obtained on myocardial perfusion changes (99 patients underwent initial PET), special lipid particles, and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment.     

The International Burden of Migraine Study (IBMS): study design, methodology, and baseline cohort characteristics

Objective: To describe a survey methodology to evaluate headache characteristics and burden and to present baseline characteristics for the international cohort of survey participants. Methods: A targeted, web-based methodology was used to recruit and survey subjects with migraine in 10 countries. Based on reported symptoms, subjects meeting ICHD-2 criteria for migraine were included; eligible subjects were classified as chronic (≥?15 headache days per month) or episodic (相似文献   

The Female Athlete Body (FAB) study: Rationale,design, and baseline characteristics

BackgroundEating Disorders (EDs) are serious psychiatric illnesses marked by psychiatric comorbidity, medical complications, and functional impairment. Research indicates that female athletes are often at greater risk for developing ED pathology versus non-athlete females. The Female Athlete Body (FAB) study is a three-site, randomized controlled trial (RCT) designed to assess the efficacy of a behavioral ED prevention program for female collegiate athletes when implemented by community providers. This paper describes the design, intervention, and participant baseline characteristics. Future papers will discuss outcomes.MethodsFemale collegiate athletes (N = 481) aged 17–21 were randomized by site, team, and sport type to either FAB or a waitlist control group. FAB consisted of three sessions (1.3 h each) of a behavioral ED prevention program. Assessments were conducted at baseline (pre-intervention), post-intervention (3 weeks), and six-, 12-, and 18-month follow-ups.ResultsThis study achieved 96% (N = 481) of target recruitment (N = 500). Few group differences emerged at baseline. Total sample analyses revealed moderately low baseline instances of ED symptoms and clinical cases.ConclusionsHealth risks associated with EDs necessitate interventions for female athletes. The FAB study is the largest existing RCT for female athletes aimed at both reduction of ED risk factors and ED prevention. The methods presented and population recruited for this study represent an ideal intervention for assessing the effects of FAB on both the aforementioned outcomes. We anticipate that findings of this study (reported in future papers) will make a significant contribution to the ED risk factor reduction and prevention literature.     

Trial of antihypertensive interventions and management: Design,methods, and selected baseline results

The Trial of Antihypertensive Interventions and Management was a multicenter randomized, placebo-controlled trial designed to assess the effectiveness of various combinations of pharmacologic and dietary interventions in the treatment of mild hypertension (diastolic blood pressure 90–100 mmHg). The primary outcome was blood pressure change between baseline and 6 months. The study consisted of a 3 × 3 factorial design wherein participants were randomly allocated to nine drug-diet treatment groups. Drugs included placebo, diuretic, and beta-blocker. Diets were usual, weight loss, and low sodium/high potassium. The basic strategy was to address clinical questions of interest by comparing mean blood pressure changes of selected drug-diet combinations. This paper describes the study including experimental design, sample size considerations, statistical analysis, organizational structure, and baseline findings.     

The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT): design and baseline characteristics

Microalbuminuria is an early marker of diabetic nephropathy and its prevention is considered key for the primary prevention of diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors and nondihydropyridine calcium channel blockers (CCBs) have specific renoprotective properties in diabetes, and preliminary evidence is available that they are more effective in combination than either of the two agents alone in limiting albuminuria either in micro- or macroalbuminuric type 2 diabetic patients. The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT) is a prospective, randomized, double-blind parallel-group study primarily aimed at evaluating the possibility of preventing the progression to microalbuminuria (urinary albumin excretion [UAE] rate 20-200 microg/min, i.e., incipient nephropathy) in 1209 hypertensive, type 2 diabetic patients with a normal UAE rate (<20 microg/min). During phase A of the study, patients are randomized to a 3-year treatment with one of the following: (1) a nondihydropyridine CCB (verapamil SR 240 mg/day); (2) an ACE inhibitor (trandolapril 2 mg/day); (3) the combination of the above study drugs (verapamil SR 180 mg/day plus trandolapril 2 mg/day); or (4) placebo. Phase B of the study evaluates the progression to macroalbuminuria (UAE> or =200 microg/min) in patients who progress to microalbuminuria in phase A or are found with microalbuminuria during the screening phase; these patients are randomized to a 2-year treatment with either trandolapril (2 mg/day) alone or verapamil SR (180 mg/day) plus trandolapril (2 mg/day). BENEDICT final results are expected to be available by the end of 2003 for phase A and 2 years later for phase B. The BENEDICT study, in addition to exploring whether primary prevention of diabetic nephropathy is an achievable goal, will also offer an opportunity to study prospectively risk factors of nephropathy and other chronic complications of type 2 diabetes. Here we provide an overview of the protocol and summarize the main baseline demographic, biochemical, and clinical characteristics of randomized participants.     

The personalized reminder information and social management system (PRISM) trial: rationale,methods and baseline characteristics

Technology holds promise in terms of providing support to older adults. To date, there have been limited robust systematic efforts to evaluate the psychosocial benefits of technology for older people and identify factors that influence both the usability and uptake of technology systems. In response to these issues, we developed the Personal Reminder Information and Social Management System (PRISM), a software application designed for older adults to support social connectivity, memory, knowledge about topics, leisure activities and access to resources. This trail is evaluating the impact of access to the PRISM system on outcomes such as social isolation, social support and connectivity. This paper reports on the approach used to design the PRISM system, study design, methodology and baseline data for the trial. The trial is multi-site randomized field trial. PRISM is being compared to a Binder condition where participants received a binder that contained content similar to that found on PRISM. The sample includes 300 older adults, aged 65–98 years, who lived alone and at risk for being isolated. The primary outcome measures for the trial include indices of social isolation and support and well-being. Secondary outcomes measures include indices of computer proficiency, technology uptake and attitudes towards technology. Follow-up assessments occurred at 6 and 12 months post-randomization. The results of this study will yield important information about the potential value of technology for older adults. The study also demonstrates how a user-centered iterative design approach can be incorporated into the design and evaluation of an intervention protocol.     

Improving palliative care through teamwork (IMPACTT) in nursing homes: Study design and baseline findings

BackgroundThe 2014 Institute of Medicine report recommended that healthcare providers caring for individuals with advanced illness have basic palliative care competencies in communication, inter-professional collaboration, and symptom management. Nursing homes, where one in three American decedents live and die, have fallen short of these competency goals. We implemented an intervention study to examine the efficacy of nursing home-based integrated palliative care teams in improving the quality of care processes and outcomes for residents at the end of life.Methods/designThis paper describes the design, rationale, and challenges of a two-arm randomized controlled trial of nursing home-based palliative care teams in 31 facilities. The impact of the intervention on residents' outcomes is measured with four risk-adjusted quality indicators: place of death (nursing home or hospital), number of hospitalizations, and self-reported pain and depression in the last 90-days of life. The effect of the intervention is also evaluated with regard to staff satisfaction and impact on care processes (e.g. palliative care competency, communication, coordination). Both secondary (e.g. the Minimum Data Set) and primary (e.g. staff surveys) data are employed to examine the effect of the intervention.DiscussionSeveral challenges in conducting a complex, nursing home-based intervention have been identified. While sustainability of the intervention without research funding is not clear, we surmise that without changes to the payment model that put palliative care services in this care setting on par with the more “skilled” care, it will not be reasonable to expect any widespread efforts to implement facility-based palliative care services.     

Women in Steady Exercise Research (WISER): Study design and methods

PurposeObservational studies have shown that physical activity is inversely associated with breast cancer etiology. WISER is a randomized controlled trial examining the effects of exercise training on oxidative stress, and hormonal and metabolic factors associated with breast cancer risk.MethodSubjects were recruited via emails, flyers, and mass media advertising. Inclusion criteria included: sedentary, age 18-30 years, non-smokers, BMI 18-40 kg/m2, not using any hormonal contraceptives. After completion of all baseline measures subjects were randomized into a control group or an exercise intervention for 4 menstrual cycles. The exercise group was asked to complete five 45 min exercise sessions per week. Exercise intensity was set at 65-70% of maximum age- predicted heart rate (max HR) and increased every four weeks. All women provided blood samples four times during the study for measurement of blood F2-isoprostanes, hormones and IGF-axis proteins. In addition, 24-hour urine samples were collected at baseline and follow-up for measurement of estrogen metabolites, as well as 24-hour food records to monitor participants' diets.DiscussionWISER consented 683 women among which 391 enrolled and 319 successfully completed the study. The overall dropout rate was 18.4% (n=72) with a higher number of participants dropping from the exercise group (n=46). No differences were found between dropouts and completers with respect to age, body weight, BMI, and demographic characteristics with the exception of degree of education. Findings from this trial will be useful in understanding the physiologic mechanisms by which exercise possibly contibutes to decreased breast cancer risk.     

The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS)

The Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) used high resolution ultrasound to compare the rate of change of carotid artery intimal medial thickness (IMT) and atherosclerosis between two groups of hypertensives receiving either isradipine or hydrochlorothiazide. This was a double blinded, active control trial that enrolled 883 patients who were followed for 3 years. Patients whose blood pressure was not controlled on the blinded medication were given open label enalapril. Inclusion criteria were either sex, mild to moderate hypertension, age >40, localized carotid arterial IMT >1.3 and <3.5 mm, LDL >130 and <189. The primary endpoint was a comparison of the change in arterial wall thickness between the two groups. This is the first trial to use ultrasound measurements of early atherosclerotic lesions as an end point. The secondary objectives were evaluation of safety, changes in blood lipids, cardiovascular events, echocardiographic left ventricular mass, and quality of life. The demographics and patient characteristics will be presented. The data on the ultrasound measurements at baseline and their relationship to patient characteristics will also be presented. This study demonstrated that the IMT could be reproducibly measured by high resolution ultrasound using a standardized scanning and reading protocol.     

Inflammation and exercise (INFLAME): study rationale, design, and methods

PurposeThe INFLAME study is designed to determine the effect of exercise training on elevated high-sensitivity C-Reactive Protein (CRP) concentrations in initially sedentary women and men.MethodsINFLAME will recruit 170 healthy, sedentary women and men with elevated CRP (≥ 2.0 mg/L) to be randomized to either an exercise group or non-exercise control group. Exercising individuals will participate in four months of supervised aerobic exercise with a total energy expenditure of 16 kcal kg^− 1 week^− 1 (KKW). Exercise intensity will be 60–80% of maximal oxygen consumption (VO₂ max).OutcomeThe primary outcome will be changed in plasma CRP concentration. Secondary outcomes include visceral adiposity, the cytokines IL-6 and TNF-α, and heart rate variability (HRV) in order to examine potential biological mechanisms whereby exercise might affect CRP concentrations.SummaryINFLAME will help us understand the effects of moderate-to-vigorous exercise on CRP concentrations in sedentary individuals. To our knowledge this will be the largest training study specifically designed to examine the effect of exercise on CRP concentrations. This study has the potential to influence therapeutic applications since CRP measurement is becoming an important clinical measurement in Coronary Heart Disease risk assessment. This study will also contribute to the limited body of literature examining the effect of exercise on the variables of visceral adiposity, cytokines, and heart rate variability.     

The Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) study: design and baseline characteristics

The Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) trial is a three-arm, randomized, placebo-controlled, double-blind study to determine the effect of tibolone 2.5 mg (Org OD 14) and continuous combined conjugated equine estrogens plus medroxyprogesterone acetate (0.625 mg/2.5 mg respectively) on progression of intima-media thickness of the carotid arteries and bone mineral density of the lumbar vertebrae and proximal femur in postmenopausal women. A total of 866 healthy postmenopausal women were recruited in six U.S. centers and five European centers. Duplicate carotid ultrasound examinations of the common carotid artery, the carotid bifurcation, and the internal carotid artery were performed at baseline. Single measurements of bone mineral density of the lumbar vertebrae and proximal femur were obtained at baseline. After randomization, ultrasound examinations were repeated every 6 months for 36 months following baseline, with a duplicate examination at the end of the study. Bone mineral density was measured every 12 months throughout the trial. The primary outcome is change in mean common carotid intima-media thickness (CIMT), defined as the average of the intima-media thickness measurements performed circumferentially at predefined angles for the near and far wall of 10-mm segments of the right and left distal common carotid arteries. Unique new features of the OPAL study are the specifically developed OPAL ultrasound protocol, yielding highly reproducible CIMT measurements, and the use of two experienced core laboratories for CIMT readings (one in the United States and one in Europe) with one common quality assurance and control program. The OPAL study is a large, placebo-controlled trial evaluating the effects of tibolone, as well as one of the first large randomized studies to determine the effects of continuous combined estrogen-progestin therapy on carotid atherosclerosis in healthy postmenopausal women. The OPAL study results are expected to complement other studies on atherosclerosis progression in healthy postmenopausal women.     

Study design,interventions, and baseline characteristics for the Substance use and TRauma Intervention for VEterans (STRIVE) trial

While comorbidity between posttraumatic stress disorder (PTSD) and substance use disorders (SUD) is common among veterans, there is debate regarding how to best treat individuals suffering from both conditions. Despite data supporting the effectiveness of integrated treatments that simultaneously address both disorders, due to concerns that an early focus on trauma may increase dropout and reduce the likelihood of achieving SUD-related goals, providers continue to prefer a sequential approach, where the addiction is treated first and PTSD treatment is instituted following sustained abstinence or reduced use. This project is designed to directly examine these provider concerns by evaluating the benefits and harms of an integrated versus a sequential approach to treating comorbid PTSD and SUD. This paper reviews the study's methodology, treatment approaches, and baseline participant characteristics. In this randomized clinical trial, one hundred eighty-three veterans with co-occurring PTSD and SUD have been randomized to one of two psychotherapies that include the same treatment components for SUD and PTSD (Motivational Enhancement Therapy and Prolonged Exposure respectively), but differ by whether the components are delivered sequentially or are integrated such that PTSD and SUD symptoms are addressed concurrently. We hypothesize that veterans assigned to integrated treatment will show greater improvement in PTSD and SUD symptoms than veterans assigned to sequential treatment. If this hypothesis is supported, the findings have the potential to change clinicians' beliefs and challenge long-standing practice patterns that require participation in SUD treatment prior to initiating trauma-focused therapies for PTSD.     

Women In Steady Exercise Research (WISER) Sister: Study design and methods

PurposeWomen at elevated risk for breast cancer are motivated to reduce their risk. Current approaches rely primarily on hormonal intervention. A preventive exercise intervention might address the same hormonal issues, yet have fewer serious side effects and less negative impact on quality of life as compared to prophylactic mastectomy. WISER Sister was a randomized controlled trial which examined effects of two doses of exercise training on endogenous sex hormone exposure, hormonally active breast tissue, and other breast cancer risk factors.MethodsSubjects for this single site trial were recruited from across the U.S., in collaboration with organizations that serve women at elevated risk, via emails, flyers, and letters. Eligibility criteria included age ≥ 18, eumenorrheic, and at elevated risk for breast cancer (e.g. BRCA1 or BRCA2 mutation and/or ≥ 18% lifetime risk according to prediction models). A 1:1:1 randomization scheme was used to allocate participants into: control, low dose (150 min/week), or high dose (300 min/week) home based treadmill exercise. Participants provided first morning urine samples daily for two menstrual cycles at study beginning and end for calculation of endogenous hormone exposure. In addition, women completed breast dynamic contrast enhanced magnetic resonance imaging, a fasting blood draw, a treadmill exercise test, and surveys at baseline and follow-up.DiscussionWISER Sister randomized 139 women, 122 of whom completed the study. The overall drop-out rate was 12%. Findings will be useful in understanding the potential for exercise to assist with reducing risk for breast cancer among women at elevated risk.     

Intervention Comparative Effectiveness for Adult Cognitive Training (ICE-ACT) Trial: Rationale,design, and baseline characteristics

Age-related perceptual and cognitive declines are associated with difficulties performing everyday tasks required to remain independent. Encouraging improvements in cognitive abilities have been shown for various short-term interventions but there is little evidence for direct impact on independence. This project compares the effect of broad and directed (narrow) technology-based training on basic perceptual and cognitive abilities in older adults and on the performance of simulated tasks of daily living including driving and fraud avoidance. Participants (N = 230, Mean age = 72) were randomly assigned to one of four training conditions: broad training using either (1) a web-based brain game suite, Brain HQ, or (2) a strategy video game, Rise of Nations, or to directed training for (3) Instrumental Activities of Daily Living (IADL) training using web-based programs for both driving and fraud avoidance training, or (4) to an active control condition of puzzle solving. Training took approximately 15–20 h for each intervention condition across four weeks. Before training began, participants received baseline ability tests of perception, attention, memory, cognition, and IADL, including a driving simulator test for hazard perception, and a financial fraud recognition test. They were tested again on these measures following training completion (post-test). A one-year follow-up from training completion is also scheduled. The baseline results support that randomization was successful across the intervention conditions. We discuss challenges and potential solutions for using technology-based interventions with older adults. We also discuss how the current trial addressed methodological limitations of previous intervention studies.Trial registration numberNCT03141281