Timing Intervention of Morning Versus Evening Exercise

Inclusion Criteria:

• Female or Male

• Age 18-55 years

• Body Mass Index 25-40 kg/m2

• Physically inactive: defined as self-reporting <150 minutes per week of physicalactivity at moderate intensity or greater on a regular basis over the past 3 months.

• No self-report of acute or chronic disease (cardiovascular disease (CVD), diabetes,gastrointestinal disorders and orthopedic problems in particular)

• No plans to relocate within the next 15 months.

• No plans for extended travel (> 2 weeks) within the next 13 months

• Live or work within 30 minutes of the Anschutz Health & Wellness Center (AHWC) (exceptions may be made at the discretion of the Study PI on a case-by-case basisfor highly motivated subjects).

• Capable and willing to give informed consent, understand exclusion criteria, acceptthe randomized group assignment, and complete outcome measures.

• No contraindications to exercise or limitations on ability to be physically active.

• Willing to be randomized to either AM or PM exercise and complete 4 exercisesessions per week.

• Own a smart phone and willing to download and use text messaging for meal intake andother related assessments.

• Willing and able to wear activity/sleep monitor for 7-14 consecutive days.

• Willing not to enroll in any other formal weight loss or physical activity programsover the next 13 months.

• Fully vaccinated, or willing to be fully vaccinated, against COVID-19 prior to studyenrollment (fully vaccinated is defined as at least 2 weeks post final vaccinedose).

• Have a primary care physician (or are willing to establish care with a primary carephysician prior to study enrollment) to address medical issues which may ariseduring screening or study procedures/interventions.

• For Females

• Not currently pregnant or lactating

• Not pregnant within the past 6 months

• Not planning to become pregnant in the next 15 months; sexually active women ofchildbearing potential may be enrolled if they have had a tubal ligation or usea reliable means of contraception

Exclusion Criteria:

• Diastolic blood pressure > 100 mm HG or systolic blood pressure > 160 mm HG.

• Resting heart rate >100

• Diabetes (fasting glucose ≥126 mg/dL or Hemoglobin A1C ≥6.5%)

• Undiagnosed hypo- or hyper-thyroidism (Thyroid Stimulating Hormone (TSH) outside ofthe normal range) or history of uncontrolled thyroid disorder. History of thyroiddisease or current thyroid disease treated with a stable medication regimen for atleast 6 months is acceptable.

• Hematocrit, white blood cell count or platelets significantly outside the normalreference range.

• Clinically significant abnormalities in hematocrit, white blood cell count orplatelets.

• Triglycerides > 400 mg/dL

• (Low Density Lipids) LDL cholesterol >200 mg/dL

• Abnormal resting electrocardiogram (ECG): serious arrhythmias, including multifocalpremature ventricular contractions (PVC's), frequent PVC's (defined as 10 or moreper min), ventricular tachycardia (defined as runs of 3 or more successive PVC's),or sustained atrial tachyarrhythmia; 2nd or 3rd degree A-V block, QTc interval > 480msec or other significant conduction defects.

• Presence or history of any metabolic or chronic health problems which would affectappetite, food intake, energy metabolism, or ability to optimally participate in theexercise component including: CVD, peripheral vascular disease, cerebrovasculardisease, significant cardiac arrhythmias or cardiac valve disease, diabetes,uncontrolled hyper- or hypothyroidism, uncontrolled hypertension, cancer (within thelast 5 years, except skin cancer or other cancers considered cured with excellentprognosis), HIV infection, significant gastrointestinal disorders (described below),significant pulmonary disorders (described below), significant renal,musculoskeletal, neurologic, hematologic, or psychiatric disease.

• Significant gastrointestinal disorders including: Crohn's disease, UlcerativeColitis, chronic diarrhea, or active gallbladder disease.

• Significant pulmonary disorders including: chronic obstructive pulmonary disease (COPD), interstitial lung disease, cystic fibrosis, or uncontrolled asthma.

• Symptoms suggestive of CVD: chest pain, shortness of breath at rest or with mildexertion, syncope.

• Regular use of prescription or over-the-counter medications known to significantlyimpact appetite, weight, sleep, or energy metabolism (e.g., appetite suppressants,lithium, stimulants, anti-psychotics, tricyclic antidepressants)

• Use of medications that would impact ability to achieve age-predicted maximum heartrate (e.g. beta blockers, cardio-selective calcium channel blockers).

• Regular use of systemic steroids (other than Oral Contraceptive Pills)

• Regular use of obesity pharmacotherapeutic agents within the last 6 months.

• Previous obesity treatment with surgery or weight loss device, except: (1)liposuction and/or abdominoplasty if performed > 1 year before screening, (2) lapbanding if the band has been removed > 1 year before screening, (3) intragastricballoon if the balloon has been removed > 1 year before screening (4)duodenal-jejunal bypass sleeve, if the sleeve has been removed > 1 year beforescreening or 5) AspireAssist or other endoscopically placed weight loss device ifthe device has been removed > 1 year before screening.

• Current alcohol or substance abuse

• Nicotine use (past 6 months)

• History of clinically diagnosed eating disorders including anorexia nervosa,bulimia, binge eating disorder. Score >20 on the Eating Attitudes Test (EATS-26) orpattern of response on the Questionnaire on Eating and Weight Patterns (QEWP-5)suggestive of possible binge eating disorder or bulimia will require furtherassessment by the Study MD to determine if it is appropriate for the subject toparticipate in the study.

• Current severe depression or history of severe depression within the previous year,based on Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteriafor Major Depressive Episode. Score > 18 on Beck Depression Inventory (BDI) willrequire further assessment by the Study MD to determine if it is appropriate for thesubject to participate in the study.

• History of other significant psychiatric illness (e.g. psychosis, schizophrenia,mania, bipolar disorder) which in the opinion of the Study MD would interfere withability to adhere to dietary or exercise interventions.

• Night-time shiftwork, rotating work, irregular sleep/wake patterns or otherscheduling constraints which may hinder ability to consistently exercise at specifictimes of the day.

• Urinary incontinence or retention (as per PI discretion based on whether degree ofincontinence/retention may impact doubly labeled water measures).

• Weight loss >5% in past 3 months.

• Weight gain >10% in past 3 months requires assessment by PI to determine reason forweight gain and if it is appropriate for the subject to participate in the study.

• Weight loss of >50 lbs in past 3 years for any reason except post-partum weight lossrequires assessment by PI to determine reason for weight gain and if it isappropriate for the subject to participate in the study.

• Currently participating in or planning to participate in any formal weight loss,dietary modification, or physical activity/exercise programs or clinical trials.