Cinnamon Bark, Water-Soluble Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus: A Randomized, Controlled Trial.

The purpose of this study is to see whether or not cinnamon or water-soluble cinnamon extract is an effective nutraceutical for the initial treatment of diabetes when compared to standard therapy of metformin.

We will recruit a total of 309 subjects who are newly diagnosed diabetics within the past month (using American Diabetes Association criteria) on no hypoglycemic medications.

Screening Visit:

• Obtain signed Informed Consent document and HIPAA Authorization.

• The following standard of care measures will be obtained:

  • Height
  • Weight
  • Blood Pressure
  • Waist circumference measured
  • Email address
  • Standard of care demographic info to include demographic, diet and activity level via the attached questionnaire.
• Women of child bearing potential will have a serum pregnancy test (approximately 1-2 teaspoons of blood) (research-driven).
• Subjects will be told to fast at least 8 hours prior to Visit 1.

Visit 1(within 1 week of screening visit):

• Subjects will have standard of care blood test drawn which include:

  • Hemoglobin A1C via 1 venipuncture (approximately 1-2 teaspoons of blood will be drawn)

    *Subjects who have had a hemoglobin A1C test within the two weeks prior to Visit 1 will not need to have this test repeated.

  • Lipid panel via 1 venipuncture (approximately 1-2 teaspoons of blood will be drawn) *Subjects who have had a lipid panel within the two weeks prior to Visit 1 will not need to have this test repeated.

• Subjects will be randomized by a non-investigator at the pharmacy. We will use a random-number generator and use blocking to ensure roughly equal sample sizes. Both subjects and investigators will be blinded to the treatment. Subjects will be randomized by the pharmacy into one of three groups:

  • Group 1: Will receive oral extended-release Metformin 1000 mg once a day for 90 days
  • Group 2: Will receive Cinnamon Bark 1000 mg once a day for 90 days
  • Group 3: Will receive Cinnulin PF 500 mg once a day for 90 days.
• Subjects will be strictly counseled to have no further diabetes medication adjustments during this time. They will receive standard of care diabetic teaching. All subjects will be permitted to initiate or continue therapy with a statin.
• Subjects will be given a 90-Day Study Diary and will be instructed to return it to the Research Staff at their next study visit.
• Subjects will be told to fast at least 8 hours prior to Visit 2.

Bi-Weekly Emails:

A study-specific email address has been established (cinnamon4treatment@yahoo.com). Subjects with access to email will be sent a monthly email. The intent of the email is to encourage adherence to study medication and to improve retention. There will be approximately 6 emails sent. The last email should include a reminder of their Final Visit 2 and a reminder to fast for at least 8 hours prior to Final Visit 2.

Final Visit 2 (after 90 days of treatment) (Visit window is between 85-105 days after Visit 1):

• Subjects will have standard of care blood test drawn which include:

  • Hemoglobin A1C via 1 venipuncture (approximately 1-2 teaspoons of blood will be drawn)
  • Lipid panel via 1 venipuncture (approximately 1-2 teaspoons of blood will be drawn) *If you have had a Lipid Panel in the two weeks prior to this visit, you will not need to have this test again. Hemoglobin A1c will have to be repeated.

• The following standard of care measures will be obtained:

  • Weight
  • Blood Pressure
  • Waist circumference measured
  • Study staff will also record whether subjects have any side effects to report.
  • Study staff will also record whether subjects increased their activity level or changed their diet via the attached questionnaire.
  • Subjects will bring in any remaining mediation to determine adherence rates to the study protocol.
• Research Staff will collect the 90-Day Study Diary and will place in the subjects' research folder.

ADHERENCE TO STUDY MEDICATION:

Adherence to study medication will be assessed via a pill count after the subject has completed Final Visit 2 and returned their study medication bottle. Subjects will be instructed to bring back all of the bottles regardless of whether there are empty or contain missed doses. Study Staff will then count any missed pills and reconcile with the "90-Day Study Diary" and record any discrepancies both in paper format and in the data collection tool.

If at any time a subject stops taking their study medication or missed a dose, Research Staff will instruct the subject that as long as they have not missed more than 18 doses (either sporadically or consecutively) that they can remain in the study and should resume taking their study medications as prescribed.

DIRECTIONS FOR TAKING MEASURMENTS:

Directions for taking waist circumference measurement: have patients take a deep breath, blow out and hold with abdominals tightened. Tell patients not to suck in their stomach. Take the measurement around the largest part of their waist. Waist Circumference should be recorded to the nearest ½ inch (for example: 40.5)

Directions for weighing subjects: have patients remove their shoes and empty their pockets of any items prior to stepping on scale. Weight should be recorded to the nearest ½ pound (for example: 150.5)

Directions for taking height: have patients remove their shoes before taking their height. Height should be recorded to the nearest 1/2 inch (for example: 60.5)

PREGNANCY:

Subjects must agree to take precautions to prevent pregnancy during the course of this study due to the possible the cinnamon bark or water soluble cinnamon extract may cause an unborn child. The only completely reliable methods of birth control are total abstinence or surgical removal of the uterus. Other methods, such as the use of condoms, a diaphragm or cervical cap, birth control pills, IUD, or sperm killing products are not totally effective in preventing pregnancy. Also, women who are breastfeeding may not participate in this study.

If a subject unintentional becomes pregnant, they will be instructed to cease study medication, return any bottles of study medication, return their 90-Day Study Diary and will be withdrawn from the study.

WITHDRAWL PROCEDURES. If at any time during the study, the subject decides to withdraw from the study, they will be referred to their Primary Care Manager (PCM) to initiate standard of care treatment. If a subject becomes pregnant during the study, they will be withdrawn from the study and referred to their PCM for standard of care treatment. If subjects are withdrawn from the study, no further testing is required.

SUBJECTS COMPLETING THE STUDY:

Subject's participation in this study is completed after Final Visit 2.

When subjects have completed the study (Visit 2), the Pharmacy will then de-identify the information and send to the Principal Investigator for analysis. Analysis described above using intention-to-treat principles for any missing data will be used (we will use the carry-forward method to impute missing data). Subjects will bring in any remaining medication to determine adherence rates to the study protocol.

OTHER ITEMS:

Standard of care diabetic education is defined as a visit with the dietician, a visit with the disease management nurse, referral to the Diabetes Conversation MAP classes to review strategies for healthy eating, the effect of eating on blood glucose and the importance of diabetes self management and/or any other diabetic education that is given as part of standard of care.

Both cinnamon bark and water soluble cinnamon extract are being given in a dose that does not increase the risk to the research subjects. Cinnamon bark and water soluble cinnamon extract are exempt from the applicability of 21 CFR 312.2(b)(i-v), Investigational New Drug Application, because the investigation is not intended to be reported to the FDA as a well-controlled study in support of a new indication for use nor intended to be used to support any other significant change in the labeling; both cinnamon bark and water soluble cinnamon extract are lawfully marketed as dietary supplements, the investigation is not intended to support a significant change in the advertising for the product; the investigation does not involve administration that significantly increases/decreases the risks associated with its use; the investigation is conducted in compliance with the requirements for institutional review set forth in part 56 and with the requirements for informed consent set forth in part 50; and the investigation is conducted in compliance with the requirements of 312.7.

• Drug: Group 1: Metformin
  Group 1: Will receive oral extended-release Metformin 1000 mg once a day for 90 days
• Dietary Supplement: Group 2: Cinnamon Bark
  Group 2: Will receive Cinnamon Bark 1000 mg once a day for 90 days
• Dietary Supplement: Group 3: Cinnulin PF
  Group 3: Will receive Cinnulin PF 500 mg once a day for 90 days.

Inclusion:

• Tricare Insurance Beneficiary (military insurance) receiving care at Nellis AFB
• Patients over the age of 18 with newly diagnosed type 2 diabetes mellitus within the last month.

Exclusion:

• Subjects who are <18 yrs of age
• Pregnant or breastfeeding
• Allergic to cinnamon or metformin
• Already taking metformin or cinnamon or other hypoglycemic medication
• Serum creatinine >1.5 (this is standard of care that would be measured by PCM upon diagnosis of type 2 diabetes mellitus)
• Initial hemoglobin A1c >9.5(this is standard of care that would be measured by PCM upon diagnosis of type 2 diabetes mellitus)