Development of A Novel Anti-Hyperglycemic Agent

This study has been terminated.
(Unable to reach accrual target.)
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00878605
First received: April 7, 2009
Last updated: October 20, 2014
Last verified: October 2014

April 7, 2009
October 20, 2014
October 2009
June 2013   (final data collection date for primary outcome measure)
Decrease of Hgb A1c [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00878605 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Development of A Novel Anti-Hyperglycemic Agent
Development of A Novel Anti-Hyperglycemic Agent

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Diabetes
  • Drug: Cyclo-Z
    Cyclo-Z is a cyclic dipeptide Cyclo (his-pro) plus zinc that may lower blood glucose
  • Drug: Placebo
    Placebo control
  • Placebo Comparator: Arm 1
    Placebo control
    Intervention: Drug: Placebo
  • Experimental: Arm 2
    Active medication
    Intervention: Drug: Cyclo-Z
  • Experimental: Arm 3
    Active medication efficacy dose
    Intervention: Drug: Cyclo-Z
  • Experimental: Arm 4
    Active medication high dose
    Intervention: Drug: Cyclo-Z
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
85
September 2013
June 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00878605
CLIN-010-08F
Yes
Department of Veterans Affairs
Department of Veterans Affairs
Not Provided
Principal Investigator: Zhaoping Li, MD VA Greater Los Angeles Healthcare System, West LA
Department of Veterans Affairs
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP