Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT)

Trial of Behavioral Weight Loss and Metformin Treatment to Lower Insulin Growth Factor in Cancer Survivors

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

Study Overview

• Status: Completed
• Conditions: Kidney Cancer; Breast Cancer; Pancreatic Cancer; Lung Cancer; Rectal Cancer; Prostate Cancer; Endometrial Cancer; Colon Cancer; Liver Cancer; Melanoma of Skin; Other Solid Malignant Tumors
• Intervention / Treatment: Behavioral: Self-control weight loss; Behavioral: Coach Directed Behavioral Weight Loss; Drug: Metformin

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21207
      • Johns Hopkins ProHealth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Self-Directed; In this group, the study staff will meet with you once at the beginning of the study to give you written information about weight management.	Behavioral: Self-control weight loss
Experimental: Coach Directed Behavioral Weight Loss; The Remote Lifestyle Coaching intervention is based on the Call Center Directed intervention to help you loss weight	Behavioral: Coach Directed Behavioral Weight Loss; Behavioral-based telephonic coaching with web-based support to promote healthy lifestyle and weight loss in overweight and obese adults.The goal of this intervention is to achieve at least 5% weight loss in the first six months of the intervention and maintain these improvements through month twelve by meeting dietary and exercise goals
Experimental: Metformin; This group will be given the study drug called Metformin. Metformin comes in tablet form that you take with meals	Drug: Metformin; Participants will receive metformin, an oral medication for type 2 diabetes.Participants randomized to the metformin intervention will receive metformin up to 2,000 mg per day.Dosing can be flexible, two or three times per day with meals as tolerated for 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IGF-1 Levels	Insulin-like growth factor (IGF)-1 levels (ng/ml) at 6 months.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IGF-1 Levels	IGF-1 at 12 months	12 months
IGF-1 to IGFBP3 Level Ratio (Molar Ratio)	IGF-1 level to IGFBP3 level ratio (molar ratio) at 6 months.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Measured by Scale(Kg)	Changes in weight among Metformin group, or coach-directed Groups versus the self-directed arm at 6 and 12 months	6 and 12 months
Body Mass Index Measured by Scale and Tap(kg/m2)	Changes in BMI among Metformin arm, or coach-directed behavioral weight loss arm versus the self-directed arm at 6 and 12 months.	6 and 12 months
EuroQol Score Assessed by Questionnaire	Changes in EuroQol score among Metformin arm, or coach-directed behavioral weight loss arm versus the self-directed arm at 6 and 12 months.	6 and 12 months
Dietary Intake Assessed by Questionnaire	Changes in dietary intake among Metformin arm, or coach-directed behavioral weight loss arm versus the self-directed arm at 6 and 12 months.	6 and 12 months
Physical Activity Amount Assessed by Questionnaire	Changes in physical activity amount among Metformin arm, or coach-directed behavioral weight loss arm versus the self-directed arm at 6 and 12 months.	6 and 12 months
Fasting Glucose Levels	Changes in fasting glucose among Metformin arm, or coach-directed behavioral weight loss arm versus the self-directed arm at 6 and 12 months.	6 and 12 months
Insulin Levels	Changes in insulin among Metformin arm, or coach-directed behavioral weight loss arm versus the self-directed arm at 6 and 12 months.	6 and 12 months
Hemoglobin A1C Levels	Changes in Hb-A1C among Metformin arm, or Coach-directed behavioral weight loss arm versus the Self-control weight loss arm at 6 and 12 months.	6 and 12 months
Interleukin (IL)-6 Levels	Changes in IL-6 among Metformin arm, or coach-directed behavioral weight loss arm versus the self-directed arm at 6 and 12 months.	6 and 12 months
Interleukin 8 Levels	Changes in IL-8 among Metformin arm, or coach-directed behavioral weight loss arm versus the self-directed arm at 6 and 12 months.	6 and 12 months
C-reactive Protein (CRP) Levels	Changes in CRP among Metformin arm, or coach-directed behavioral weight loss arm versus the self-directed arm at 6 and 12 months.	6 and 12 months
Side Effects Assessed by Side Effect Questionnaire	assessing side effect among Metformin arm, or coach-directed behavioral weight loss arm versus the self-directed arm at 6 and 12 months.	6 and 12 months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Maryland Cigarette Restitution Fund
• Investigators: Principal Investigator: Jessica Yeh, PhD, Johns Hopkins University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: April 21, 2015
• First Submitted That Met QC Criteria: April 30, 2015
• First Posted (Estimate): May 1, 2015

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: August 26, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Kidney Neoplasms; Endometrial Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: J14148; IRB00035653 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO