Development of A Novel Anti-Hyperglycemic Agent

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00878605
First received: April 7, 2009
Last updated: February 11, 2013
Last verified: February 2013
  Purpose

The purpose of this clinical trial is to test the effectiveness and safety of a new anti-diabetes drug (Cyclo-Z) for the prevention and treatment of Type 2 diabetes. This study will determine dose-dependent efficacy and safety of this new drug for the treatment of human diabetes. The Food and Drug Administration has granted approval for the use of this investigational product to be used in a study (FDA approval IND #: 61,897). This new drug is thought to work by increasing the amount of zinc in your body, which in turn should improve your sugar metabolism. If this study successfully proves that Cyclo-Z is effective for the treatment of diabetes and is without significant side effects, a large, multi-center study of diabetic patients will then be performed.


Condition Intervention Phase
Diabetes
Drug: Cyclo-Z
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Development of A Novel Anti-Hyperglycemic Agent

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Decrease of Hgb A1c [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: October 2009
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm 1
Placebo control
Drug: Placebo
Placebo control
Experimental: Arm 2
Active medication
Drug: Cyclo-Z
Cyclo-Z is a cyclic dipeptide Cyclo (his-pro) plus zinc that may lower blood glucose
Experimental: Arm 3
Active medication efficacy dose
Drug: Cyclo-Z
Cyclo-Z is a cyclic dipeptide Cyclo (his-pro) plus zinc that may lower blood glucose
Experimental: Arm 4
Active medication high dose
Drug: Cyclo-Z
Cyclo-Z is a cyclic dipeptide Cyclo (his-pro) plus zinc that may lower blood glucose

Detailed Description:

We have demonstrated that a cyclic dipeptide Cyclo (his-pro) plus zinc (Cyclo-Z) treatment improved clinical conditions of diabetes in various animal models and a phase 1 clinical trial. The main objective of this study is to demonstrate that this product is safe and effective for the treatment of human diabetes.

Research Plan This is a randomized, double blinded, placebo-controlled, and parallel study. In this study, we will recruit 120 hypoglycemic drug na ve type 2 diabetic patients and randomize them into 4 groups of 30 subjects each to compare the effects of a Cyclo-Z capsule containing CHP 0 (placebo), 3 mg (minimally effective), 9 mg (optimally effective), or 15 mg (no-additional effect) plus 20 mg zinc on diabetic symptoms in a 12-week trial period. The primary outcome of this study is improvement of hemoglobin A1c; secondary outcomes are fasting blood glucose, 2 hours postprandial glucose and glucose tolerance test. Safety will be assessed by the presence of severe adverse events (SAEs), adverse events (AEs), any changes of vital signs, physical exams, blood hematology, chemistry, liver, renal, thyroid function tests, urine analysis and zinc, copper levels.

Clinical Significance The proposed study has a direct impact on veteran's healthcare service. The applicant has obtained two types of US and international patent approvals for preventing and treating human diabetes and obesity with Cyclo-Z. One patent application for Alzheimer's disease treatment has just been approved. These patent rights are now assigned to the DVA. Based on our background studies and observation we anticipate the proposed Phase 2a clinical trials will prove that Cyclo-Z treatment is safe and effective for the treatment of human diabetes and we will be able to present a new class of anti-diabetes drug to improve healthcare of both the VA diabetic patients and the general public.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. History of type 2 diabetes mellitus who are na ve to hypoglycemic treatment, inadequately controlled by diet and exercise alone or oral medications.
  2. Hemoglobin A1c level of 6.5 % to 8.0 % inclusive. Subjects not taking hypoglycemic drugs with HgbA1c of 6.0% to 6.5% must have a diagnosis of DM.
  3. Fasting blood glucose levels reasonably stable for at least 2 months or during the two-week lead-in-period.
  4. Ethnicity: All ethnic groups.
  5. Gender: Both men and women.
  6. Female with reproductive potential must not be pregnant or lactating, and using reliable contraception methods.
  7. Age >18 years old.

Exclusion Criteria:

  1. Taking insulin.
  2. History of diabetic ketoacidosis or hyper osmolar non-ketotic coma.
  3. Diabetes Mellitus related end-organ damage:

    • Evidence of diabetic autonomic and peripheral neuropathy
    • Diabetic proliferative retinopathy, based on eye exam by ophthalmologist
    • Diabetes nephropathy defined by > 500 mg/24 hour urinary albumin excretion
  4. Any disease likely to limit life span and/or increase risks of interventions:

    • Screening carotid B-mode ultrasound indicating clinically significant stenos in the common carotid arteries requiring intervention by angioplasty or resection.
    • Cancer treatment in the past 5 years, with the exception of cancers that have been cured, and carry a good prognosis.
    • Infectious disease: HIV positivity, active tuberculosis, or pneumonia.
  5. Cardiovascular disease:

    • Hospitalization for treatment of heart disease in the past 12 months.
    • New York Heart Association Functional Class > 2.
    • Left Bundle branch block on EKG.
    • Third degree atrioventricular block on EKG.
    • Uncontrolled hypertension with average systolic blood pressure of > 160 mmHg on two screening visits and diastolic blood pressure > 95 mmHg on two screening visit.
    • Pulse rate > 95 beats per minute on both screening visits.
    • Stroke or transient ischemic attack in the past 12 months.
  6. Gastrointestinal disease:

    • Chronic hepatitis or cirrhosis.
    • Episode of alcoholic hepatitis or alcoholic pancreatitis.
    • Inflammatory bowel disease requiring treatment in the past 12 months.
    • Recent or significant abdominal surgery (e.g. gastrectomy, gastric bypass).
  7. Renal disease: Serum creatinine > 1.5 mg/dL for men, and > 1.4 mg/dL for women.
  8. Lung disease:

    • Chronic obstructive airway disease or asthma requiring daily therapy.
    • Use of home oxygen.
  9. Anemia: Hematocrit of < 36.0% in men or < 33% in women.
  10. Conditions or behaviors likely to affect the conduct of the study

    • Unable or unwilling to give informed consent.
    • Unable to communicate with the clinic staff.
    • Unwilling to accept treatment assignment by randomization.
    • Weight loss of > 10% in the past 6 months.
    • Unable to walk without any assisted device.
    • Major psychiatric disorder which would impede conduct of the research.
    • Excessive alcohol intake (more than 2 drinks/day)
  11. Medications

    • Psychoactive agents such as Monoamine oxidase inhibitors and Antidepressive agents (lithium, prozac, zoloft, serzone, paxil, efflexor)
    • Systemic use of glucocorticoids steroids within previous 6 weeks.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00878605

Locations
United States, California
VA Greater Los Angeles Healthcare System, West LA
West Los Angeles, California, United States, 90073
Sponsors and Collaborators
Investigators
Principal Investigator: Zhaoping Li, MD VA Greater Los Angeles Healthcare System, West LA
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00878605     History of Changes
Other Study ID Numbers: CLIN-010-08F
Study First Received: April 7, 2009
Last Updated: February 11, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
Diabetes
Cyclo-Z

Additional relevant MeSH terms:
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014