Clinical trial NCT02431676: Survivorship Promotion In Reducing IGF-1 Trial
Official title: Trial of Behavioral Weight Loss and Metformin Treatment to Lower Insulin Growth Factor in Cancer Survivors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Prostate Cancer
Lung Cancer
Colon Cancer
Melanoma of Skin
Endometrial Cancer
Liver Cancer
Pancreatic Cancer
Rectal Cancer
Kidney Cancer
Other Solid Malignant Tumors
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Maryland Cigarette Restitution Fund
First posted: 2015-05-01
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a prospective, single-center randomized trial with three arms, and an allocation ratio of 1:1:1. The study design is an efficacy study to evaluate the effect of metformin and coach-directed behavioral weight loss versus self-directed weight loss on insulin-like growth factor (IGF)-1 and IGF-1 to THE IGFBP-III ratio blood levels after 6 and 12 months of intervention. The coach-directed Behavioral Weight Loss arm is a web-based remote delivery and communication system that promotes healthy behavioral changes. The Metformin arm is a pharmaceutical intervention of oral metformin. This is a secondary prevention study for men and women who have survived solid malignant tumors


Eligibility criteria: Inclusion Criteria:

* Women and men ages 18 or older
* Have been previously diagnosed with a malignant solid tumor, completed their required surgical, and/or chemotherapy and/or radiation curative intent therapy at least three months prior to enrollment, and have an anticipated treatment-free life span of 12 months or longer. Chemoprophylaxis with tamoxifen or aromatase inhibitors for breast cancer in women and anti- Luteinizing hormone-releasing hormone (LHRH) therapy for prostate cancer in men will be permitted.
* Have a BMI of 25 kg/m\^2 or greater and weight \<=400 lbs.
* Willingness to accept randomization to each of the three arms
* Willingness to change diet, physical activity, and weight
* Regular access to computer with a reliable Internet connection
* Ability to send and receive emails
* Ability to complete online forms
* Access to phone
* Willingness to provide written informed consent

Exclusion Criteria:

* Women who are breastfeeding, pregnant, or planning pregnancy within the next year
* Medication-treated diabetes
* Fasting blood glucose \>=200 mg/dL, or fasting blood glucose \>=126 and \<200 mg/dL and HbA1C \>=7%
* Current or prior regular use of metformin within the past 3 months
* Uncontrolled concurrent medical condition likely to limit compliance with the study interventions
* Received any chemotherapy (unless anti-hormonal therapy) and/or radiation three months or less prior to the proposed intervention date
* Have a prior history of lactic acidosis by self-report
* Prior or planned bariatric surgery
* Have significant renal disease or dysfunction defined as Estimated glomerular filtration rate (eGFR)\<45
* Have significant hepatic dysfunction \[Aspartate aminotransferase (AST)/Alanine transaminase (ALT) ≥ 2 x upper limit of normal (ULN) or reported liver disease\]
* Self-reported average consumption of \> 14 alcoholic drink per week
* Currently enrolled or planned to enroll in weight loss program
* Hemoglobin \<9 g/dl
* Platelet count \<100
* White blood cell count (WBC) \<2.5
* Plans to relocate from the area within one years
* Use of prescription weight loss medication(s) (e.g., lorcaserin, topiramate/phentermine, phentermine, liraglutide, and bupropion/naltrexone), including off label use of drugs for weight loss or over-the-counter weigh loss medications such as Orlistat within the past 6 months.

Primary outcomes:
measure: IGF-1 Levels
timeFrame: 6 months
Secondary outcomes:
measure: IGF-1 Levels
timeFrame: 12 months
measure: IGF-1 to IGFBP3 Level Ratio (Molar Ratio)
timeFrame: 6 months
Other outcomes:
measure: Weight Measured by Scale(Kg)
timeFrame: 6 and 12 months
measure: Body Mass Index Measured by Scale and Tap(kg/m2)
timeFrame: 6 and 12 months
measure: EuroQol Score Assessed by Questionnaire
timeFrame: 6 and 12 months
measure: Dietary Intake Assessed by Questionnaire
timeFrame: 6 and 12 months
measure: Physical Activity Amount Assessed by Questionnaire
timeFrame: 6 and 12 months
measure: Fasting Glucose Levels
timeFrame: 6 and 12 months
measure: Insulin Levels
timeFrame: 6 and 12 months
measure: Hemoglobin A1C Levels
timeFrame: 6 and 12 months
measure: Interleukin (IL)-6 Levels
timeFrame: 6 and 12 months
measure: Interleukin 8 Levels
timeFrame: 6 and 12 months
measure: C-reactive Protein (CRP) Levels
timeFrame: 6 and 12 months
measure: Side Effects Assessed by Side Effect Questionnaire
timeFrame: 6 and 12 months
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins ProHealth
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Jessica Yeh, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tilves C, Yeh HC, Maruthur N, Juraschek SP, Miller E, White K, Appel LJ, Mueller NT. Increases in Circulating and Fecal Butyrate are Associated With Reduced Blood Pressure and Hypertension: Results From the SPIRIT Trial. J Am Heart Assoc. 2022 Jul 5;11(13):e024763. doi: 10.1161/JAHA.121.024763. Epub 2022 Jun 22.
citation: Tilves C, Yeh HC, Maruthur N, Juraschek SP, Miller ER, Appel LJ, Mueller NT. A behavioral weight-loss intervention, but not metformin, decreases a marker of gut barrier permeability: results from the SPIRIT randomized trial. Int J Obes (Lond). 2022 Mar;46(3):655-660. doi: 10.1038/s41366-021-01039-2. Epub 2022 Jan 6.
citation: Hu JR, Yeh HC, Mueller NT, Appel LJ, Miller ER 3rd, Maruthur NM, Jerome GJ, Chang AR, Gelber AC, Juraschek SP. Effects of a Behavioral Weight Loss Intervention and Metformin Treatment on Serum Urate: Results from a Randomized Clinical Trial. Nutrients. 2021 Jul 31;13(8):2673. doi: 10.3390/nu13082673.
citation: Mueller NT, Differding MK, Zhang M, Maruthur NM, Juraschek SP, Miller ER 3rd, Appel LJ, Yeh HC. Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial. Diabetes Care. 2021 Jul;44(7):1462-1471. doi: 10.2337/dc20-2257. Epub 2021 May 18.
citation: Juraschek SP, Plante TB, Charleston J, Miller ER, Yeh HC, Appel LJ, Jerome GJ, Gayles D, Durkin N, White K, Dalcin A, Hermosilla M. Use of online recruitment strategies in a randomized trial of cancer survivors. Clin Trials. 2018 Apr;15(2):130-138. doi: 10.1177/1740774517745829. Epub 2018 Jan 24.