Clinical trial NCT05944731: Use of Continuous Glucose Monitoring Devices Among People Living With Type 1 Diabetes in Kenya.
Official title: Use of Continuous Glucose Monitoring Devices Among People Living With Type 1 Diabetes in Kenya: A Three-arm Pragmatic Randomized Study on the Effectiveness, Feasibility, Acceptability, and Cost.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Type 1 Diabetes
Keywords: Continuous Glucose Monitoring Devices
Lead sponsor: Foundation for Innovative New Diagnostics, Switzerland
Sponsor class: OTHER
Collaborators: name: The Leona M. and Harry B. Helmsley Charitable Trust
name: Kenya Diabetes Management and Information Centre (DMI)
First posted: 2023-07-13
Enrollment: 246
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Three arm pragmatic randomized controlled study
Primary purpose: DIAGNOSTIC

Brief summary: Diabetes mellitus (diabetes) is a chronic condition that represents a major public health and clinical concern. Self-monitoring of blood glucose (SMBG) is a critical part of the care of individuals with diabetes. SMBG entails capillary fingerstick blood glucose testing multiple times per day. Many people with diabetes find this testing painful and cumbersome, often resulting in poor compliance to a glucose self-monitoring schedule. Furthermore, SMBG only provides limited visibility on daily and nightly glucose profiles, meaning that hypo- and hyperglycaemic episodes can be missed or detected with delay. The use of minimally invasive continuous glucose monitoring devices (CGMs) in diabetes management circumvents these challenges as CGMs measure glucose every few minutes over a period of 1-2 weeks through a sensor with a fine needle that is inserted once into a user's arm or abdomen. This enables periodic glucose measurement without repeat finger pricks and provides the user with a detailed glucose profile over the entire wear time of the sensor, thus enabling better adjustment of therapy or behaviour.

In populations where CGMs are accessible to people with diabetes as standard of care and without additional cost, many people with type 1 diabetes have switched from SMBG via fingerstick to the use of CGMs permanently, using the devices continuously. This is rarely possibly for people with type 1 diabetes in the public sector in LMICs as CGMs are not provided as standard of care. Little data on effectiveness, feasibility, acceptability, and cost of the use of CGMs in LMIC populations is available to inform clinical models for the integration of CGMs into diabetes management. Furthermore, it has not been investigated if intermittent, as opposed to continuous use of CGMs provides clinical benefit. Intermittent use could be beneficial for people with diabetes who do not have the means to pay for continuous use of CGMs.

This study aims to evaluate the effectiveness, feasibility, acceptability, and cost of intermittent and continuous use of CGM among people with type 1 diabetes in Kenya.

Detailed description: Study Design As this study is a PrCT the study aspects will be embedded in the normal clinical care delivery of diabetes care in the selected clinics. Introducing only 1 additional clinic visit and 1 additional qualitative visit for study related procedures. The primary outcome measure, HbA1c, will be assessed through the HbA1c testing that is already used in these clinics. It is important to note that the type of HbA1c test (i.e.: laboratory-based vs point-of-care) per participant must remain constant during the study, this is because of variability of performance between various HbA1c testing platforms.

General Design This is a three-arm pragmatic randomized control study. The expected duration of study participants involvement in the study is 15 months, this consists of 9 months of intervention with a follow up visit 6 months post the last interventional study visit.

* Arm 1 is those participants randomized to use of CGM in a continuous fashion; CGM use for the duration of 9 months.
* Arm 2 is those participants randomized to intermittent use of CGM; CGM use for 4 time points consisting of 2 weeks of CGM use each, for the duration of 9 months.
* Arm 3 is those participants randomized to standard of care; regular use of self-monitoring of blood glucose (SMBG) for the duration of 9 months.

For all participants the first study visit will consist of:

1. Enrolment including ICF,
2. Baseline surveys including demographics and the Glucose Monitoring Satisfaction Survey
3. randomized assignment to study arm,
4. blood draw for HbA1c testing.

For those randomized to Arm 3 the clinicians visit will take place during enrolment visit. For those randomized to Arm 1 and Arm 2 they will receive an education session on the CGM, be provided with the CGM, and be guided how to self-apply the CGM during enrolment visit.

During all Study Follow Up visits participants will have blood drawn for HbA1c testing, complete a brief survey to capture any hospitalizations and/or hypoglycaemic events related to diabetes complications that occurred between study visits. During Study Follow up visit C participants will complete HRQOL surveys.

Detailed explanation of the study visits per arm are outlined below by arm in section Qualitative methods used across all arms will consist of focus group discussions (FGDs) among the participants and caregivers of participants. Approximately 15 participants above the age of 18 years old will be selected from each arm (n=45, 3 FGD in total) and approximately 15 participants age range of 11 to 17 years old will be selected from each arm (n=45, 3 FGD in total) to participate in arm specific FGD to take place 30 to 35 weeks after study enrolment started. These FGDs will focus on understanding participant perceptions towards their current glucose monitoring devices and quality of life. To capture the perspectives of care givers of children and adolescents living with T1 diabetes 15 caregivers will be selected from each arm (n=45, 3 FGD in total) to participate in arm specific FGDs to take place 30 to 35 weeks after study enrolment started. These FGDs will focus on understanding care giver perspectives towards their charge's glucose monitoring devices and quality of life from the perspective of the care giver as well as their perceptions towards the quality of life for their charge.

Qualitative methods will also be used to gather perceptions from the healthcare providers regarding their perceptions surrounding the feasibility and acceptability of use of CGMs in their settings. This will consist of a semi-structured interviews (SSI) of selected HCW (n"10 total) to be conducted after week 36 after study enrolment started.

Arm 1 Continuous use of CGM For those in Arm 1 there will be 6 clinical study visits for all participants. There will be an additional visit for a FGD among a subset of participants.

1. Enrolment visit: For those randomized to Arm 1 they will receive an education session on the CGM, be provided with the CGM, blood will be drawn for HbA1c testing, and be guided how to self-apply the CGM during enrolment visit.
2. The second study visit will take place 1 week after the enrolment visit. During this second visit the participant will see the clinician and review the CGM data from the first week. Participants in Arm 1 will be provided with 7 additional CGMs such that they have one CGM extra CGM on hand as a spare if any issue arises with a CGM and needs to be replaced, and 6 to continually use the CGM devices until their third study visit (Study Follow up A) to take place at the end of 11 weeks after enrolment.
3. Study Follow up A: At the third study visit participants will see the clinician and review the CGM data from the period of time in between second study visit and current, blood will be drawn for HbA1c testing, and the participant will be provided with 6 additional CGMS such that the continually use the CGM devices until their fourth study visit (Study Follow up B) to take place at the end of 23 weeks after enrolment.
4. Study Follow up B: At the fourth study visit participants will see the clinician and review the CGM data from the period of time in between third study visit and current, blood will be drawn for HbA1c testing, and the participant will be provided with 6 additional CGMS such that they continually use the CGM devices until their fifth study visit (Study Follow up C) to take place at the end of 35 weeks after enrolment.
5. Study Follow up C: At the fifth study visit participants will see the clinician and review the CGM data from the period in between fourth study visit and current, blood will be drawn for HbA1c testing and the participant will be provided with 1 additional CGM to use for the week following Study follow up C.
6. Study Follow up D: At the sixth and final study visit which takes place at the end of week 57 from enrolment study participants will see the clinician and blood will be drawn for HbA1c.

Arm 2 Intermittent use of CGM For those in Arm 2 there will be 6 clinical study visits for all participants. There will be an additional visit for a FGD among a subset of participants.

1. Enrolment visit: For those randomized to Arm 2 they will receive an education session on the CGM, be provided with the CGM, blood will be drawn for HbA1c testing, and be guided how to self-apply the CGM during enrolment visit.
2. The second study visit will take place 1 week after the enrolment visit. During this second visit the participant will see the clinician and review the CGM data from the first week. Participants in Arm 2 will be provided with 2 additional CGMs, one CGM to have on hand as a spare if any issue arises with a CGM and needs to be replaced and 1 such that they use 1 CGM for the week directly following the clinician visit and 1 week before their third study visit (Study Follow up A) to take place at the end of 11 weeks after enrolment.
3. Study Follow up A: At the third study visit participants will see the clinician and review the CGM data from the preceding week before Study follow up A, blood will be drawn for HbA1c testing, and the participant will be provided with 1 additional CGM such that the participant uses the CGM for the week directly following Study follow up A and 1 week before their fourth study visit (Study Follow up B) to take place at the end of 23 weeks after enrolment.
4. Study Follow up B: At the fourth study visit participants will see the clinician and review the CGM data from the preceding week before Study follow up B, blood will be drawn for HbA1c testing, and the participant will be provided with 1 additional CGM such that the participant uses the CGM for the week directly following Study follow up A, and 1 week before their fifth study visit (Study Follow up C) to take place at the end of 35 weeks after enrolment.
5. Study Follow up C: At the fifth study visit participants will see the clinician and review the CGM data from the week preceding Study Follow up C, blood will be drawn for HbA1c testing and the participant will be provided with 1 additional CGM to use for the week following Study follow up C.
6. Study Follow up D: At the sixth and final study visit which takes place at the end of week 57 from enrolment study participants will see the clinicals and blood will be drawn for HbA1c.

Arm 3 Standard of Care For those in Arm 3 there will be 5 clinical study visits for all participants. There will be an additional visit for a FGD among a subset of participants. Participants will follow the standard of care at each clinic.

1. Enrolment visit: Those participants randomized to Arm 3 will see their clinician at the enrolment visit as per SoC. Blood will be drawn for HbA1c testing.
2. Study Follow up A: the second study visit will take place at the end of 11 weeks after enrolment, participants will see the clinician as per SoC. Blood will be drawn for HbA1c testing.
3. Study Follow up B: the third study visit will take place at the end of 23 weeks after enrolment. participants will see the clinician as per SoC. Blood will be drawn for HbA1c testing.
4. Study Follow up C: the fourth study visit will take place at the end of 35 weeks after enrolment. Participants will see the clinician as per SoC. Blood will be drawn for HbA1c.
5. Study Follow up D: the fifth and final study visit will take place at the end of 57 weeks after enrolment. participants will see the clinician as per SoC. Blood will be drawn for HbA1c.

Scientific Rationale for Study Design As this study intendeds to generate evidence to inform policy and decision makers on the potential benefits of use of CGM in Kenya a pragmatic, rather than an explanatory, randomized control study design was selected. A PrCT design was selected as the study aims to understand the impact of CGM use in as close to real world settings as possible. A classically designed randomized control trial with overly strict study criteria and processes may lead results that are not directly translatable to real world experience, while a classical RCT may have strong internal validity often RCTs are criticized for a lack of external validity, therefore a PrCT design was selected to balance internal and external validity. A PrCT design may "provide more realistic effect size estimates and enhance translation of research findings into clinical practice".

Eligibility criteria: Inclusion Criteria:

Recipient of care participants are eligible to be included in the Study only if all the following inclusion criteria apply:

1. People living with T1 diabetes with HbA1c levels ≥10% (with at least 1 measurement over 18 months prior to study enrolment) who are attending for diabetes care at the 3 study clinics.

Care givers to children/adolescents living with T1 diabetes are eligible to be included in the study only if all the following inclusion criteria apply:

1. The child/adolescent that the person is a care giver to is enrolled in the study.

Healthcare providers are eligible to be included in the study only if all the following inclusion criteria apply:

1. Healthcare provider at the study sties engaged in diabetes care provision related to the study.

Exclusion Criteria:

Participants are excluded from the Study if any of the following exclusion criteria apply:

1. People living with type 1 diabetes under 4 years of age
2. People diagnosed with Type 1 diabetes within the last 2 years.
3. People who have used a CGM in the last 18 months prior to enrollment
4. People living with type 2 diabetes.
5. Known pregnancy at the time of study enrolment.

Primary outcomes:
measure: Impact of continuous and intermittent CGM used on blood glucose levels in comparison to standard of care in people living with type 1 diabetes
timeFrame: 15 months
Secondary outcomes:
measure: Impact of continuous and intermittent CGM use on the stability of blood glucose concentrations related to diabetes
timeFrame: 15 months
measure: Impact of continuous and intermittent CGM use on unplanned visits to outpatient clinics and/or hospital related to diabetes complications.
timeFrame: 15 months
measure: Acceptability and feasibility of continuous and intermittent CGM use from a healthcare provider, recipients of care & care givers perspective
timeFrame: 15 months
measure: Cost of continuous and intermittent CGM from a user and provider perspective
timeFrame: 15 months
Other outcomes:
Locations:
Study officials:
affiliation: FIND, the global alliance for diagnostics
name: Beatrice Vetter
role: STUDY_DIRECTOR
References:
citation: Maiorino MI, Signoriello S, Maio A, Chiodini P, Bellastella G, Scappaticcio L, Longo M, Giugliano D, Esposito K. Effects of Continuous Glucose Monitoring on Metrics of Glycemic Control in Diabetes: A Systematic Review With Meta-analysis of Randomized Controlled Trials. Diabetes Care. 2020 May;43(5):1146-1156. doi: 10.2337/dc19-1459.
citation: Lind M, Polonsky W, Hirsch IB, Heise T, Bolinder J, Dahlqvist S, Schwarz E, Olafsdottir AF, Frid A, Wedel H, Ahlen E, Nystrom T, Hellman J. Continuous Glucose Monitoring vs Conventional Therapy for Glycemic Control in Adults With Type 1 Diabetes Treated With Multiple Daily Insulin Injections: The GOLD Randomized Clinical Trial. JAMA. 2017 Jan 24;317(4):379-387. doi: 10.1001/jama.2016.19976.
citation: Beck RW, Riddlesworth T, Ruedy K, Ahmann A, Bergenstal R, Haller S, Kollman C, Kruger D, McGill JB, Polonsky W, Toschi E, Wolpert H, Price D; DIAMOND Study Group. Effect of Continuous Glucose Monitoring on Glycemic Control in Adults With Type 1 Diabetes Using Insulin Injections: The DIAMOND Randomized Clinical Trial. JAMA. 2017 Jan 24;317(4):371-378. doi: 10.1001/jama.2016.19975.
citation: Welsh JB, Gao P, Derdzinski M, Puhr S, Johnson TK, Walker TC, Graham C. Accuracy, Utilization, and Effectiveness Comparisons of Different Continuous Glucose Monitoring Systems. Diabetes Technol Ther. 2019 Mar;21(3):128-132. doi: 10.1089/dia.2018.0374. Epub 2019 Jan 25.
citation: Brown JVE, Ajjan R, Siddiqi N, Coventry PA. Acceptability and feasibility of continuous glucose monitoring in people with diabetes: protocol for a mixed-methods systematic review of quantitative and qualitative evidence. Syst Rev. 2022 Dec 9;11(1):263. doi: 10.1186/s13643-022-02126-9.
citation: McClure Yauch L, Velazquez E, Piloya-Were T, Wainaina Mungai L, Omar A, Moran A. Continuous glucose monitoring assessment of metabolic control in east African children and young adults with type 1 diabetes: A pilot and feasibility study. Endocrinol Diabetes Metab. 2020 Jun 8;3(3):e00135. doi: 10.1002/edm2.135. eCollection 2020 Jul.
citation: Palmer T, Jennings HM, Shannon G, Salustri F, Grewal G, Chelagat W, Sarker M, Pelletier N, Haghparast-Bidgoli H, Skordis J. Improving access to diabetes care for children: An evaluation of the changing diabetes in children project in Kenya and Bangladesh. Pediatr Diabetes. 2022 Feb;23(1):19-32. doi: 10.1111/pedi.13277. Epub 2021 Dec 3.
citation: Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe KE, Zwarenstein M. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ. 2015 May 8;350:h2147. doi: 10.1136/bmj.h2147. No abstract available.
citation: Hohenschurz-Schmidt DJ, Cherkin D, Rice ASC, Dworkin RH, Turk DC, McDermott MP, Bair MJ, DeBar LL, Edwards RR, Farrar JT, Kerns RD, Markman JD, Rowbotham MC, Sherman KJ, Wasan AD, Cowan P, Desjardins P, Ferguson M, Freeman R, Gewandter JS, Gilron I, Grol-Prokopczyk H, Hertz SH, Iyengar S, Kamp C, Karp BI, Kleykamp BA, Loeser JD, Mackey S, Malamut R, McNicol E, Patel KV, Sandbrink F, Schmader K, Simon L, Steiner DJ, Veasley C, Vollert J. Research objectives and general considerations for pragmatic clinical trials of pain treatments: IMMPACT statement. Pain. 2023 Jul 1;164(7):1457-1472. doi: 10.1097/j.pain.0000000000002888. Epub 2023 Mar 22.
citation: Cohen J. Statistical Power Analysis for the Behavioral Sciences Second Edition. 1988.
citation: Gamerman V, Cai T, Elsäßer A. Pragmatic randomized clinical trials: best practices and statistical guidance. Health Serv Outcomes Res Methodol 2019; 19: 23-35.
citation: Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009 Nov;41(4):1149-60. doi: 10.3758/BRM.41.4.1149.
citation: Bowen GA. Naturalistic inquiry and the saturation concept: a research note. Qualitative Research 2008; 8: 137-152.