An Open-Label Pilot Intervention Trial to Prevent Diabetes in Prediabetic Adult Survivors of Childhood Cancer

NCT04742751 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: PREDMR21CA261713
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in survivor, single-arm pilot study with the goal of establishing evidence of feasibility and safety of a combined pharmacologic (metformin) and lifestyle intervention (using an existing digital platform) to prevent diabetes in prediabetic adult survivors of childhood cancer. Primary Objective The primary aim of this proposal is to establish the feasibility and safety of a 24-week combined metformin + intensive lifestyle intervention among adult survivors with prediabetes (including a 12-week lifestyle alone run-in followed by 12-week combined intervention among survivors remaining prediabetic). Primary endpoints of this trial will be adherence to 1) daily metformin administration and 2) completion of required core-curriculum of the lifestyle change intervention. Safety will be assessed using the Global Rating of Side Effects Burden Secondary Objectives The secondary aim is to assess preliminary evidence for efficacy of the combined metformin + intensive lifestyle intervention on glycemic control and insulin resistance. Glycemic control will be measured by fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) and insulin resistance measured by the homeostatic model assessment (HOMA-IR) and IGF- binding protein 1 (IGF-BP1; a measure of insulin sensitivity strongly correlated with euglycemic insulin clamp testing). Exploratory Objectives To assess preliminary evidence for efficacy of the combined metformin + intensive lifestyle intervention on weight, other anthropometric measures, blood pressure and lipid profile, physical activity (self-reported and as measured by accelerometer), frailty measures, and health-related quality of life (HRQOL). We will also assess diabetes development at future SJLIFE visits. To assess measures of participation in the lifestyle change program as well as barriers to participation and medication adherence.

Conditions

PreDiabetes; Adult Children

Outcome Measures

Primary Outcomes (16)

• Adherence for feasibility

  Adherence to the intervention with 80% adherence to prescribed metformin and completion of 60% of the digitally-delivered core education curriculum through the lifestyle change platform.

  2 years

• Digitally-delivered core education curriculum through the lifestyle change platform

  Adherence will be monitored by completion logs of lessons

  At end of Week 24

• Safety and Adverse Events (Symptom Log including monitoring for AEs)

  An Adverse Event Monitoring Log with Global Rating of Side Effects Burden

  Week 4

• Safety and Adverse Events (Symptom Log including monitoring for AEs)

  An Adverse Event Monitoring Log with Global Rating of Side Effects Burden

  Week 8

• Safety and Adverse Events (Symptom Log including monitoring for AEs)

  An Adverse Event Monitoring Log with Global Rating of Side Effects Burden

  Week 12

• Safety and Adverse Events (Symptom Log including monitoring for AEs)

  An Adverse Event Monitoring Log with Global Rating of Side Effects Burden

  Week 14

• Safety and Adverse Events (Symptom Log including monitoring for AEs)

  An Adverse Event Monitoring Log with Global Rating of Side Effects Burden

  Week 16

• Safety and Adverse Events (Symptom Log including monitoring for AEs)

  An Adverse Event Monitoring Log with Global Rating of Side Effects Burden

  Week 20

• Safety and Adverse Events (Symptom Log including monitoring for AEs)

  An Adverse Event Monitoring Log with Global Rating of Side Effects Burden

  Week 24

• Drug adherence/Pill Counts

  Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.

  Week 2

• Drug adherence/Pill Counts

  Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.

  Week 4

• Drug adherence/Pill Counts

  Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.

  Week 8

• Drug adherence/Pill Counts

  Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.

  Week 12

• Drug adherence/Pill Counts

  Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.

  Week 16

• Drug adherence/Pill Counts

  Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.

  Week 20

• Drug adherence/Pill Counts

  Adherence will be monitored by pill counts showing participant taking study drug, metformin ER, 80% of the time.

  Week 24

Secondary Outcomes (2)

• Glycemic Control

  Baseline to Week 24 (on campus labs at Baseline, Week 12 and 24)

• Glycemic Control

  Baseline to Week 24 (on campus labs at Baseline, Week 12 and 24

Study Arms (1)

Treatment

EXPERIMENTAL

Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With Metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.

Drug: Metformin; Behavioral: Digital Intervention

Interventions

Metformin DRUG

To begin week 12 for participants who remain prediabetic after 12 week lifestyle run-in. Dosage and Route of Administration: 500 mg dose/ day to be taken orally, increased to 1000 mg dose/ day at week 14 through week 24. The dose should be taken immediately following the evening meal and at approximately the same time daily

Also known as: D-Care DM2, Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet, Metformin ER

Treatment

Digital Intervention BEHAVIORAL

Lifestyle Change Digital Intervention - This is a digital platform that will include a core curriculum focused on diet, exercise, and behavioral strategies for goal setting and self-monitoring to improve diet including a weight loss On Day 1, participants will begin their digital lifestyle intervention using their smart-phone application with their lifestyle coach and peer group. On day 14, participants will be contacted by phone (+/- 4 days, day 10 to 18) and adherence assessed using virtual pill counts via phone calls. At weeks 4, 8, 16 and 20 a phone-based pill count for adherence and adverse event symptom log will be completed and study medication dispensed. At week 12 (interim assessment) and 24 (study-end), the participant will return to St. Jude Children's Research Hospital (SJCRH) for an in-person assessment. The digital lifestyle change program will complete at week 24.

Also known as: Lifestyle Change Digital Intervention

Treatment

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Investigators will recruit to enroll 55 survivors who are at least 18 but \<45 years of age who participate in the St. Jude Lifetime Cohort Study (SJLIFE) and have been identified to have prediabetes defined as hemoglobin A1c (HbA1c)
• Participant in SJLIFE
• ≥18 and \<45 years of age
• Prediabetic: fasting plasma glucose 105-125 mg/dL, hemoglobin A1c 5.7- 6.4% (either or both criteria may be present) According to institutional and NIH policy, the study will accession research participants regardless of sex and ethnic background. Institutional experience confirms broad representation in this regard.

You may not qualify if:

• Absence of treatment related diabetes risk. Survivors will be excluded if their cancer treatment required observation only, surgery alone not involving the abdomen or brain, radiation alone not involving the chest (pancreatic risk), abdomen or brain (e.g. retinoblastoma treated with enucleation alone, melanoma of an extremity treated with excision alone, neuroblastoma in an infant requiring observation only)
• Diabetes at baseline assessment: FPG ≥126 mg/dL, HbA1c ≥6.5% or previous diagnosis by a physician (except gestational diabetes that resolved post-partum)
• BMI \<19 kg/m2
• Current metformin use (including for any period ≥30 days in the past 1yr)
• Known allergy to metformin
• Current use of other oral glucose lowering medications, non-insulin injectable diabetes medications or insulin (Appendix)
• Current participation in a lifestyle change program
• Chronic kidney disease ≥ stage IIIb (eGFR \< 45 mL/min)
• Severe cardiovascular disease or recent intervention (NYHA class ≥2 or heart failure hospitalization in the past 6mo, Aortic stenosis, Heart block including LBBB or 3rd degree AV block, SBP \>180 or DBP \>105 mmHg, myocardial infarction or coronary revascularization in the past 1 month)
• Severe hepatic dysfunction: cirrhosis or AST/ALT \>3 times upper limit of normal
• Pulmonary disease with dependence on oxygen or daily use of bronchodilators
• Weight loss \>10% in the past 6 months
• Bariatric surgery in the past 2 years
• Pregnant, within 3 months post-partum, nursing, or planning to become pregnant
• Anemia: hematocrit \<36% in males or \<33% in females

Sponsors & Collaborators

• Conquer Cancer Foundation: collaborator
• National Cancer Institute (NCI): collaborator
• St. Jude Children's Research Hospital: lead
• St. Baldrick's Foundation: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Prediabetic State

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Stephanie Dixon, MD, MPH

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: The schema was changed the to an adaptive trial design with a 12 week lifestyle run-in followed by a combined metformin+lifestyle intervention for 12 weeks
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: February 8, 2021
• Study Start: March 2, 2022
• Primary Completion: January 16, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (1)