Clinical trial NCT04742751: An Open-Label Pilot Intervention Trial to Prevent Diabetes in Prediabetic Adult Survivors of Childhood Cancer
Official title: An Open-Label Pilot Intervention Trial to Prevent Diabetes in Prediabetic Adult Survivors of Childhood Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: PreDiabetes
Adult Children
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: St. Baldrick's Foundation
name: Conquer Cancer Foundation
name: National Cancer Institute (NCI)
First posted: 2021-02-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Eligible subjects who meet inclusion criteria will be enrolled in a 12 week run-in period of the digital lifestyle intervention program. At the 12 week study visit, those who remain prediabetic will received metformin extended release daily, first at lower dose (500 mg/day) to minimize gastrointestinal side effects (diarrhea, nausea, flatulence, bloating), then escalated to a maximum dose of 1000 mg/day at week 14. The digitally delivered lifestyle change program will include a core curriculum focused on diet quality, food types, exercise and behavioral strategies for goal setting, and self- monitoring.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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
* Ongoing alcohol or substance abuse using criteria from the AUDIT and DAST questionnaires (Appendix)
* Diagnosis of schizophrenia or other psychotic disorder
* Vision impairment limiting ability to interface with the digital program
* Unable to swallow medication
* Non-English speaking
* Cognitive impairment defined by IQ \<80
* Current active cancer or undergoing treatment for active cancer

Primary outcomes:
measure: Adherence for feasibility
timeFrame: 2 years
measure: Digitally-delivered core education curriculum through the lifestyle change platform
timeFrame: At end of Week 24
measure: Safety and Adverse Events (Symptom Log including monitoring for AEs)
timeFrame: Week 4
measure: Safety and Adverse Events (Symptom Log including monitoring for AEs)
timeFrame: Week 8
measure: Safety and Adverse Events (Symptom Log including monitoring for AEs)
timeFrame: Week 12
measure: Safety and Adverse Events (Symptom Log including monitoring for AEs)
timeFrame: Week 14
measure: Safety and Adverse Events (Symptom Log including monitoring for AEs)
timeFrame: Week 16
measure: Safety and Adverse Events (Symptom Log including monitoring for AEs)
timeFrame: Week 20
measure: Safety and Adverse Events (Symptom Log including monitoring for AEs)
timeFrame: Week 24
measure: Drug adherence/Pill Counts
timeFrame: Week 2
measure: Drug adherence/Pill Counts
timeFrame: Week 4
measure: Drug adherence/Pill Counts
timeFrame: Week 8
measure: Drug adherence/Pill Counts
timeFrame: Week 12
measure: Drug adherence/Pill Counts
timeFrame: Week 16
measure: Drug adherence/Pill Counts
timeFrame: Week 20
measure: Drug adherence/Pill Counts
timeFrame: Week 24
Secondary outcomes:
measure: Glycemic Control
timeFrame: Baseline to Week 24 (on campus labs at Baseline, Week 12 and 24)
measure: Glycemic Control
timeFrame: Baseline to Week 24 (on campus labs at Baseline, Week 12 and 24
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Stephanie Dixon, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: