Clinical trial NCT03660553
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes Elderly Insulin treatment Quality of life
Sponsor: University of Miami
Start date: 2018-10-10; Completion date: 2022-06-30
Enrollment: 7 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Basal-bolus insulin therapy, which includes one injection of long acting insulin and three injections of short acting insulin is the most commonly used insulin treatment. However, many older patients find the basal-bolus insulin regimen hard to manage because it involves 4 injections and 4 blood glucose tests each day. It is possible that a simplified treatment that involves one injection of long acting insulin daily and two blood glucose tests daily might be equally effective. This simplified regimen, if effective, would be easier to use and might result in less errors. Therefore, the investigators want to conduct this study to compare using a single daily injection of basal insulin with the usual basal-bolus insulin regimen in elderly patients (age \>65 years) with type 2 diabetes.

Detailed description:

Arms: arm 1: MSI group will receive four insulin injections per day that will include a long acting and a short acting insulin. Short acting insulin will be either insulin aspart or insulin lispro. arm 2: BI group will receive only one injection of insulin glargine in the morning.
Interventions: intervention 1: Insulin Glargine intervention 2: Insulin Glargine intervention 3: Insulin Aspart intervention 4: Insulin Lispro
Intervention descriptions: intervention 1: 0.40 units/kg body weight intervention 2: 0.20 units/kg body weight intervention 3: 0.20 units/kg body weight intervention 4: 0.20 units/kg body weight

Protocol documents:
Prot_SAP_001.pdf: 
 
Effect of simplified insulin regimen on glycemic control and quality of life in an elderly 
population with type 2 diabetes 
06/14/2023 
NCT03660553 
 
 
 
 
      


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1) Protocol Title 
Effect of simplified insulin regimen on glycemic control and quality of life in an elderly 
population with type 2 diabetes 
 
2) IRB Review History* 
 
Not applicable, the protocol has not been submitted for review by an external 
IRB. 
3) Objectives* 
Primary objective of this study is to test the hypothesis that once daily basal insulin 
(BI) is non-inferior to multiple subcutaneous injections (MSI) of insulin for glycemic 
control (HbA1c) in elderly patients with T2DM. A secondary aim of this study is to 
test that BI is superior to MSI for lowering HbA1c and is associated with lower 
incidence of hypoglycemia. 
 
4) Background* 
 
The prevalence of type 2 diabetes mellitus (T2DM) has been increasing over 
time, especially in the older age groups. According to the latest CDC data, 25.2% of 
the US population >65 years old has diabetes and it is expected to grow due to 
increase in life span as well as increase in incidence of T2DM [1, 2]. Many patients in 
this age group have other co-morbidities like heart disease, renal insufficiency, 
cognitive impairment, and lack of social support among others [3]. Elderly patients 
with T2DM are at an increased risk of hypoglycemia. Moreover, the benefits of tight 
glycemic control have not been established in this age group. Taking these factors into 
consideration, many professional organizations (American Diabetes Association, 
American Geriatrics Society) recommend relaxed glycemic goals (HbA1c ~8%) in the 
elderly population [4]. However, even for these relatively relaxed glycemic goals, 
insulin treatment is often necessary because due to associated comorbidities, many 
patients in this age group are poor candidates for non-insulin antidiabetic agents 


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[5]. Moreover, elderly patients with long standing T2DM may have decreased beta 
cell function and respond poorly to non-insulin antidiabetic agents [5]. 
 
Currently, basal-bolus insulin therapy that includes one injection of long acting 
insulin and three injections of meal-time short acting insulin is the most commonly 
used insulin regimen. However, many older patients find the basal-bolus insulin 
regimen hard to manage due to the need of multiple injections and frequent blood 
glucose testing, especially in the setting of impaired vision, poor physical function and 
cognitive impairment [7]. If unsupervised, there are more errors with this regimen 
that can lead to hypoglycemia and hospitalization. Moreover, basal-bolus insulin 
regimen is stressful and expensive for the elderly patients, as well as time consuming 
for their care-givers. Many experts have tried a simplified regimen of basal insulin 
alone in the elderly patients (unpublished). In our experience, this simplified regimen 
is associated with less errors, improved glycemic control and dramatic improvement 
in the quality of life for the patient as well as their care-givers, without compromising 
glycemic control. However, there are no systematic studies comparing simplified 
insulin regimen versus the basal-bolus insulin regimen. We propose a study 
comparing single injection of basal insulin versus the usual basal-bolus insulin 
regimen in elderly patients (age >65 years) with T2DM. We believe this study will 
help in improving clinical care of elderly patients with T2DM and save healthcare 
costs. 
 
 
5) Inclusion and Exclusion Criteria* 
 
Inclusion Criteria 
• Age >65 years 
• Patient treated with an insulin regimen 
Exclusion Criteria 


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• Unable to provide informed consent 
• Enrollment in another research study 
• History of hypoglycemia unawareness 
• Pregnant women 
• Prisoners 
 
 
 
6) Number of Subjects* 
 
We plan to recruit a total of 44 subjects from the outpatient clinic of the 
University of Miami including Diabetes Research institute and the Lennar 
Foundation Medical Center. We also recruit patients from the clinics at the 
Jackson Health System. 
 
 
7) Study-Wide Recruitment Methods* 
 
Subjects will be recruited from the outpatient clinics of the University of Miami and 
Jackson Health affiliated clinics. Treating providers must have provided permission 
to include their patients into the study. The treating physician will identify the 
potential subject by screening through the clinic records or during the clinic visit. The 
study will be first introduced to potentially eligible patients by their treating 
physicians. After the treating physician speaks to the patient and if the patient agrees 
to be part of the study, the treating physician will refer the patient to the study team 
via verbal contact, phone contact, secure email or HER message. A member of study 
team will then speak with the patient and explain the study. This will take place either 
during the patient’s clinic visit or over the phone. If the patient remains interested, 
patient chart will be accessed to screen for inclusion / exclusion criteria. If the patient 
qualifies for the study, a copy of the informed consent will be given or mailed. The 
patients will be encouraged to discuss participation with their primary care 
providers. They will be asked to call back if they have any questions.  The consent 


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form will be signed at the time of first study visit that would often coincide with the 
patient’s clinic visit. 
 
Study Timelines 
 
Patients will be recruited over a period of one year, 09/01/2018 – 8/31/2022. 
All patients will be followed for a period of 6 month. The estimated date to 
complete the primary analysis will be 06/2023. 
 
 
8) Study Endpoints* 
Primary endpoint: Hemoglobin A1c (HbA1c) at 6 months after enrollment. 
 
 
Secondary endpoint: 1. Average blood glucose levels (BG) during the study, 2. 
Incidence of hypoglycemia defined as any reported BG <70 mg/dl, 3. Incidence of 
severe hypoglycemia defined as any BG <54 mg/dl or patient requiring assistance to 
recover from hypoglycemia. 
 
9) Procedures Involved* 
Subject Enrollment 
 
Subjects will be recruited from the outpatient clinics of the University of Miami and 
Jackson Health ACC clinics. Treating providers will inform the patients about the 
study. If a patient shows interest in participation, the study staff will review patient’s 
chart for inclusion / exclusion criteria and provide the patient with more information 
about the study. Those, eligible for study and willing to participate, will have to 
provide a written informed consent. 
 
Study Plan 


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This will be a randomized controlled trial of elderly patients with T2DM currently 
inadequately controlled on an insulin regimen. After an informed consent, patients 
will be randomized in 1:1 ratio to either a control group (MSI) or a study group (BI). 
MSI group will receive four insulin injections per day that will include a long acting 
and a short acting insulin. BI group will receive only one injection of insulin glargine 
in the morning. The goal of treatment in both groups will be achieving an HbA1c <8% 
without any incidence of hypoglycemia. The study period after randomization will be 
6 months. 
Both groups will receive instructions about diet and exercise and all 
other treatments as per the current ADA standards. Patients will be advised to send 
their blood glucose data to the study team every 3-7 days. In addition, patients will be 
asked to complete the questionnaires for quality of life measures and patient 
satisfaction at baseline and after 6 months of treatment. 
 
Insulin doses 
 
The BI group will receive insulin glargine at a dose of 0.40 units/kg body weight 
once a day in the morning. If the total daily dose is more than 80 units, we will split 
the dose into two equal doses given morning and evening. The patient will be advised 
to monitor blood glucose (BG) four times daily: before meals and bedtime. The dose 
of insulin will be increased by 2 units every 3rd day to bring down the bedtime BG to 
<200 and fasting BG <130 mg/dL. Any BG <70 mg/dL or complaints of hypoglycemic 
symptoms at any time will lead to a decrease in insulin dose by 2 units or more. 
 
The MSI group will receive insulin at a dose of 0.40 unit/kg body weight given 
50% as insulin glargine at bedtime and 50% as rapid acting insulin divided into three 
doses before each major meal. The patient will be advised to monitor blood glucose 
(BG) four times daily: before meals and bedtime. The dose of insulin glargine will be 
adjusted every 3rd day to keep the fasting BG in 70-130 mg/dl range. The meal-time 


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rapid acting insulin doses will be adjusted to keep the pre-lunch and pre-dinner BGs 
<180 and bedtime BG <200 mg/dl. 
 
10) Data and Specimen Banking* 
 
The data or specimens will not be banked. 
 
11) Data Management* 
 
Statistical Analysis 
Baseline characteristics will be summarized and compared to assure that the 
randomization algorithm resulted in comparable groups. Distributions will be 
evaluated and transformations to approximate normality will be considered if 
skewed. The main analysis will be an independent sample t-test or an analysis of 
covariance to allow for the inclusion of possible covariates such as age, baseline A1C, 
duration of diabetes, oral anti-diabetic medication use at baseline and number of 
comorbidities. 95% two-sided confidence interval (calculated on the basis of t-test or 
analysis of covariance) for the difference between BI and MSI treatment will be used 
for interpreting the results with regard to the non-inferiority margin. The main 
outcome variable will be the HbA1c after 6 months of treatment. Secondary outcomes 
will include mean glucose levels, hypoglycemic events, quality of life measures, 
patient satisfaction, and treatment failure. 
The power calculation is based on the assumption that BI regimen will be non- 
inferior to MSI regimen for glycemic control. We anticipate that mean HbA1c in the 
control group (MSI group) at the end of treatment period will be 8.0% with standard 
deviation of 0.9. The study is designed to demonstrate a non-inferiority margin of 0.5, 
which is well within the margin of clinical relevance for this population. Group 
sample sizes of 18 in each group will achieve 95% power to detect non-inferiority 
using a two-sided, two-sample t-test with alpha 5%. Assuming a 20% drop-out rate, 
we plan to enroll 44 subjects into this study. 


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12) Provisions to Monitor the Data to Ensure the Safety of Subjects* 
 
 
Follow-up and Laboratory test 
 
Patients will be required to send their BG data to the study team every 3 days 
while the insulin doses are being adjusted and then every 1-2 weeks. Communication 
will be arranged via secure patient portal emails, telephone or clinic visits. HbA1C will 
be obtained at randomization and every 3 months after enrollment into the study. 
. 
 
13) Withdrawal of Subjects* 
 
Subject withdrawal criteria 
- 
Patient with severe hypoglycemia needing assistance or BG below 54 ng/dl 
after two insulin dose adjustments. 
- 
Patient who develops hyperosmolar hyperglycemic syndrome. 
- 
Patient with uncontrolled hyperglycemia >400 despite two insulin dose 
adjustments. 
- 
Pregnancy during the study 
 
 
14) Risks to Subjects* 
 
A relatively large dose of insulin glargine given in the morning may increase the 
risk of hypoglycemia. We will monitor patients closely and decrease the insulin dose 
as needed to prevent hypoglycemia. Any severe hypoglycemia in the BI group after 
two dose adjustments will lead to withdrawal from the study and conversion of 
insulin regimen to MSI. 


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There is also a risk of less tight glycemic control in the BI group as compared to 
the MSI group. However, a relatively high HbA1c is unlikely to cause any harm within 
the study period. Patients unable to achieve a lower HbA1c as compared to the 
baseline within first 3 months of the study will be withdrawn from the BI group and 
placed on MSI regimen. 
 
15) Potential Benefits to Subjects* 
 
Glucose control is likely to improve in all patients participating in this study. The main 
research intervention in this study will be decreasing the number of insulin injection 
to once daily instead of multiple daily injections. The remaining outpatient care for 
diabetes will be as per the ADA guidelines. Knowledge gained from this study may help 
simplify treatment of diabetes for the elderly patients with T2DM 
 
16) Vulnerable Populations* 
 
 
Children, incarcerated people and individuals with impaired decision-making 
capacity will be excluded from participating in the study. The study includes 
only the patients aged >65 years. Therefore, women of childbearing potential 
are excluded from this study. In spite of this, if a woman becomes pregnant, 
she will be immediately excluded from the study. However, we will follow 
them during the pregnancy for any potential complications that may be related 
to the study. Students and employees of the University of Miami are eligible 
for the study. Before they agree to participate, the students will be explained 
that their decision not to participate or to withdraw from the study will not affect 
their grades. Employees of the University of Miami will be explained that their 
decision not to participate or to withdraw from the study will not affect their 
employment at the University of Miami 


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17) Sharing of Results with Subjects* 
 
The results of the study will be published in a peer review journal. If the results show 
that the BI group has significantly better outcomes, patients in the MSI group will be 
informed and given the option of change in their insulin regimen. 
 
18) Setting 
 
 
The outpatient clinic of the University of Miami including Diabetes Research 
institute and the Lennar Foundation Medical Center and Jackson Health 
Clinics. 
 
19) Resources Available 
 
The diabetes clinics at the University of Miami are well equipped to recruit patients 
into clinical trials. All staff involved in this study have completed CITI training. The 
PI has extensive experience in clinical research. The PI has a furnished office with 
locked cabinets, a private phone-line and password protected computer with all the 
necessary software. The study will be conducted at the investigators’ own time. 
 
 
 
 
20) Recruitment Methods 
 
Subjects will be recruited from the outpatient clinics of the University of Miami 
affiliated clinics. Treating providers must have provided permission to include their 
patients into the study. The inclusion/exclusion criteria will be applied to identify 
appropriate subjects. Either the treating physician will identify the potential subject 
or a member of the study team will identify the potential subject by screening through 


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the clinic schedule. The study will be first introduced to potentially eligible patients 
by their treating physicians. If they agree to obtain more information, a member of 
study team will speak with the patient and explain the study. If the patient shows 
willingness to participate, a copy of the informed consent will be given. The patients 
will be encouraged to discuss participation with their primary care providers. They 
will be asked to call back if they have any questions. The consent form is signed only 
at the time of first visit study visit that would often coincide with the patient’s clinic 
visit. 
 
21) Local Number of Subjects 
 
 
We plan to recruit 44 subjects into this study. 
 
 
22) Confidentiality 
 
Each subject will be assigned a study ID, and all study-related measurements and 
information will be stripped of subject identifiers. Data will be used only in aggregate, 
and no identifying characteristics of individuals will be published or presented. Data 
will be stored for a period of seven years after completion of the study. 


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Choose the statements below that are applicable to this research: 
 
(a). Will the research collect protected health information or personally identifiable 
information from the EMR or from subjects at UHealth and/or JHS? 
Yes (If checked go to 26(b)) 
No (If checked, go to Section 27) 
 
(b). Check the box next to the correct statement below 
☒ Research Subjects will sign a HIPAA Authorization before the research will collect 
this data. 
☐ Research Subjects will not sign a HIPAA Authorization for this data collection and 
the research is requesting a waiver of HIPAA authorization from the IRB. 
 
(c). How will the research store the data? 
☒ On a University of Miami electronic device (e.g. encrypted, password-protected 
computer) 
On a cloud-based storage system that is approved by the University of Miami 
On the secured JHS SharePoint environment 
Other, specify: Click here to enter text. 
 
(d) Select one of the following: 
☐ The Principal Investigator (and/or Study Team members) will record (e.g. write 
down, abstract) data acquired in a manner that does not include any indirect or direct 
identifiers (listed in the instructions for Section 26 of this protocol), and the recorded data 
will not be linked to the individual’s’ identity. 
OR 
☒ The Principal investigator (and/or Study Team members) will record (e.g. write 
down, abstract) the data collected in a manner that does not include any direct identifiers 
(see list in the instructions for Section 26 of this protocol) of any subject. Instead, the 
Principal Investigator and/or Study Team members shall will assign a code (that is not 
derived in whole or in part from any direct or indirect identifiers of the individual) to 
each study subject and link the code to the study subject’s identity. The link to each 
subject’s identity and/ or other identifiable information will be maintained on a document 
separate from the research data. 
 
(e) Additional requirement for Jackson Health System Data: 
 Not-applicable, no data will be acquired from JHS under a waiver of authorization. 
 
JHS data, including Protected Health Information (PHI) and/or Personally Identifiable 
Information (PII), acquired from JHS for this research under a waiver of authorization shall 
only be stored on the secured JHS SharePoint environment made available by JHS. I and 
the Study Team members shall not copy or store the JHS sourced personally identifiable 
☒ 
☒ 
☐ 
☒ 
☐ 


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information (PII), including protected health information (PHI) data to any other system, 
including any systems maintained or provided by the University of Miami. I and the Study 
Team shall only copy or transfer JHS-sourced data that has been properly de-identified in 
accordance with all requirements contained in the HIPAA Rules by removing all of the 
identifiers listed in the instructions for Section 26 of this protocol. 
 
23) Provisions to Protect the Privacy Interests of Subjects 
 
Data will be confidentially collected from study participants and will only be 
used for research purposes. All paper records will be kept in locked file 
cabinets at 5555 Ponce de Leon Blvd, Suite 344B, Coral Gables, FL 33146. All 
participant data stored in electronic form (UM approved cloud service) will be 
in folders that are password protected. Data confidentiality will be maintained 
and regulations regarding access to data by those other than the study staff 
will be followed. The code identification data will be kept in a locked file 
available only to the study doctors and staff unless requested by the 
appropriate regulatory authority 
 
24) Compensation for Research-Related Injury 
 
There will be no compensation for study related injuries. 
 
25) Economic Burden to Subjects 
 
The only research related intervention in this study is the change in the number of 
insulin injections. All other procedures, medications and testing supplies are part of 


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the standard care, and medically necessary for these patients. There will no research- 
related economic burden to the subjects in this study. 
 
26) Consent Process 
 
The Human Research Committee/Ethics Committee shall approve the consent form. 
It will include all elements required by FDA, state and local regulations, as well as any 
additional elements relevant to specific study situations. 
 
The study will be completely explained to each prospective candidate and the subject 
must give consent by signing and dating the approved informed consent form. The 
Investigator will provide the subject with a copy of the consent form that is in a 
language that he or she understands. 
 
Before study initiation, this protocol and the informed consent form will be submitted 
for review and approval to Health Sciences Institutional Review Board /Ethics 
Committee charged with this responsibility. 
 
27) Process to Document Consent in Writing 
 
 
One of the investigators will explain the study to the subject, answer any question 
and if the subject agrees to participate, an informed consent will be sought from the 
potential subject. We will follow the IRB guidelines for interaction with subjects and 
procedures for obtaining informed consent. The consent form will be reviewed in 
detail with each subject, and all questions will be answered. Subjects will be given as 
much time as they want to read, review, and complete the consent form. Subjects who 
prefer contemplating their decision for days or weeks or who wish to discuss their 
participation in the study with others (family members, friends, physician), will be 
encouraged to do so. We will stress that participation in our research study is 
voluntary, that subjects may withdraw from the study at any time, and that the 


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investigators reserve the right to discontinue the research protocol at any time. A 
copy of the signed informed consent form will be given to each subject. For the non- 
English speaking subjects, IRB policy on obtaining and documenting informed 
consent of subjects who do not speak English will be followed. 
28) Drugs or Devices 
 
 
The study does not involve drugs or devices that we plan to store, handle or 
administer to the subjects.