EFFECTS OF MOXIFLOXACIN AND GEMIFLOXACIN ON BLOOD GLUCOSE AND ECG MORPHOLOGY OF EUGLYCEMICS:A CLINICAL STUDY
Condition: Blood Glucose, Low; Hypoglycemia
MeSH terms: Hypoglycemia
Study type: Interventional
Phase: Phase 1

Summary: 
      EFFECTS OF MOXIFLOXACIN AND GEMIFLOXACIN ON BLOOD GLUCOSE LEVEL OF EUGLYCEMICS:A PRE-CLINICAL
      AND CLINICAL STUDY.

      Our aim and objectives are to:

        1. To check the possible effects of Moxifloxacin and Gemifloxacin in healthy volunteers for
           possible effects on blood glucose levels with a subsequent shift in serum insulin level
           of healthy volunteer (target population).

        2. ECG morphology effect. In the above entitled studies we are going to determine the
           effects of the above two 4th generation fluoroquinolones drugs on the blood glucose
           levels and ECG morphology effect.of euglycemics healthy volunteers.The drug will be gave
           as per approved standard adult dose.The drug is FDA approved and marketed drug.No risk
           is to the patient only 3-5 ml of the blood will be taken at baseline and after the drug
           completion at steady state concentration.
    

Detailed description: 
      The study will be conducted under good clinical practice guidelines and a consent form will
      be signed from the healthy volunteers as per design of World health organization.The study
      has no harmful effects on the heaths of the volunteers as we are conducting the study for
      five dose/one pack drug will be gaven. The volunteers will be sampled randomly and the effect
      of the said drugs will be determined on blood glucose and insulin level.

      Diabetes mellitus (DM), a non-communicable disease, which is considered now-a-days a life
      threatening disease to the human health (1,2).According to the report of International
      Diabetes Federation (IFD) and World Health Organization (WHO), diabetes mellitus is one of
      the World's fifth leading cause of mortality and about 415 million people of the world's
      population have diabetes mellitus in 2018 (3). After every 6 seconds, a person dies from
      diabetes mellitus (4, 5). Pakistan is a country with 7th highest diabetic population in the
      world and it is assumed to rise to 4th highest place by 2030 (6). Due to sedentary life style
      of People, there is a maximum increase of DM in the last decade (7). DM is classified into
      two classes i.e. Type I and Type II (8). The Type I diabetes is much more common. It is due
      to defective insulin secretion or insulin action or both (9). The Type II diabetes is
      now-a-days attributed to genetic disorders affecting the beta cells of the pancreas (10), or
      the ability of body cells to respond to insulin action leading to insulin resistance DM (11,
      12).

      Fluoroquinolones (FQs) are a group of antibacterial antibiotics. Newer fluoroquinolones has
      expanded its traditional coverage from Gram-negative coverage to Gram-positive as well as to
      anaerobic organisms (14-16). It has been used since 2-3 decades and has been observed to have
      excellent anti-microbial coverage, but unfortunately the FQs are associated with adverse drug
      events including strong dysglycemic effects which has also led to irreversible brain damage
      and even death (17). Till date, six different types of adverse drug reactions have been
      reported with Fluoroquinolones. These include prolongation of QT interval, Photo toxicity,
      hepatotoxicity and alteration in the blood glucose hemostasis (hyperglycemia or sometimes
      hypoglycemia), damage to the tendons leading to tendinitis (18). Canadian Adverse Drug
      Reaction Monitoring Program (CADRMP) reported that three marketed fluoroquinolones namely
      gatifloxacin, levofloxacin and moxifloxacilin are under Metabolic and Nutritional Disorders
      category. Among them Temafloxacin, levofloxacin and gatifloxacin have been reported to be
      associated with hemolysis (19).

      It has been assumed that the dysglycemic effects of FQs mainly occur through their action on
      the ATP- sensitive K + channels. According to definition, an agent that causes the selective
      relaxation of an induced contractility due to low K+ (20-25 mM) is grouped as K+ channel
      opener. From the studies it can be assumed that fluoroquinolones may block the ATP-sensitive
      K+ channels as well as the opening of as Calcium channels that are voltage dependent (22).
      These opened Calcium channels further depolarize the membrane potential ultimately releasing
      insulin. These Studies reveals that fluoroquinolones have pancreatic beta cell cytotropic
      activity, however the dysglycemic effects of Moxifloxacin and Gemifloxacin have not been
      proven but very strong associations have been demonstrated via some case report studies (21).

      Keeping in view all these studies and developments regarding the adverse effects associated
      with fluoroquinolones specially the dysglycemic effects due to cytotropic influence on the
      beta cells of the pancreas it is now very much needed to actually correlate these effects
      seen in the beta cells of the pancreas with the pancreatic tissue histopathological changes.
      Since, Moxifloxacin and Gemifloxacin are a new generation quinolones, thus our study focuses
      on them to get a clear picture of its possible shift of blood glucose and insulin in our
      society. Thus the hallmark of our study is to focus on dysglycemic effects (either
      hyperglycemic or hypoglycemic effects) associated with quinolones, it is not clear to get a
      clear picture on blood glucose level until it is tested in control environment of a
      preclinical study, and to translate the possible effects of the preclinical study in a
      controlled clinical trial of healthy volunteers who are euglycemics as well.
    

Intervention name(s): Moxifloxacin 400mg; Gemifloxacin 320 MG
Intervention type(s): Drug; Drug
Intervention description(s): Blood will be checked for glucose levels and ECG at Baseline(Day Ist) and at Steady state Steady state(Tmax) via Glucometer and ECG machine will be used for determination of serum insulin levels.; Blood will be checked for glucose levels and ECG at Baseline(Day Ist) and at Steady state(Tmax) via Glucometer and ECG machine will be used for determination of serum insulin levels.
Other intervention name(s): Blood glucose and serum insulin; Blood glucose and serum insulin
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Moxifloxacin; Gemifloxacin
Allocation: Randomized
Intervention model: Single Group Assignment
Intervention model description: Single group for Moxifloxacin having 30 healthy euglycemic volunteers, another group for Gemifloxacin having 30 healthy euglycemic volunteers
Masking: Double (Participant, Investigator)
Primary purpose: Screening
Keywords: ,Blood glucose,Serum insulin