Reaction products of sodium glucoheptonate with zinc sulfate and sodium hydroxide

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

November 1997 to February 1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Effect of Treatment with Zinc Gluconate or Zinc Acetate on Experimental and Natural Colds

Author:

Turner, R. B., Cetnarowski, W. E.

Year:

2000

Bibliographic source:

Clinical Infectious Diseases 2000; 31:1202-8

Materials and methods

Study type:

self-reporting of symptoms

Endpoint addressed:

acute toxicity: oral

repeated dose toxicity: oral

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Two clinical trials were conducted, one involving 273 subjects with experimental rhinovirus colds and the other involving 281 subjects with natural colds. Symptomatic volunteers were randomized to receive oral lozenges containing zinc gluconate (13.3 mg), zinc acetate (5 or 11.5 mg), or placebo.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Bis(D-gluconato-O1,O2)zinc

EC Number:

224-736-9

EC Name:

Bis(D-gluconato-O1,O2)zinc

Cas Number:

4468-02-4

Molecular formula:

C12H22O14Zn

IUPAC Name:

zinc bis(2,3,4,5,6-pentahydroxyhexanoate) (non-preferred name)

Details on test material:

13.3 mg

Specific details on test material used for the study:

- Zinc Gluconate (lozenges, 13.3 mg)

Method

Type of population:

general

Ethical approval:

not specified

Details on study design:

A total of 554 subjects were tested, of which 273 were challenged with rhinovirus type 39 and 281 presented a common-cold. The rhinovirus and the common-cold group were divided in four subgroups which received different treatments. Either the subject was treated with oral lozenges containing zinc gluconate (13.3 mg), zinc acetat (5 or 11.5 mg), or placebo.
Subjects were asked to judge the maximum severity of 7 symptoms—sneezing, rhinorrhea, nasal obstruction, sore throat, cough, headache, and hoarseness—occurring in the interval since the last symptom evaluation. Before each patient was randomized to treatment, the symptom scores were recorded in an interactive interview with the study staff once each day, and symptom scores for the 7 individual symptoms were summed to yield the total daily symptom score. After randomization to treatment, the symptom scores were recorded by the subject at »12-h intervals, just prior to the first and the last daily doses of study medication. The morning and evening symptom scores were averaged to provide a daily symptom score.
All subjects who met enrollment criteria for the study were challenged with rhinovirus type 39 and then isolated in hotel rooms for the next 5 days. Subjects were randomized to receive study medication 24 h after challenge if they had a total daily symptom score >3. Subjects who did not meet this symptom criterion were reassessed 48 h after challenge and randomized if they had a total daily symptom score >3. Subjects who did not have a symptom score >3 at one of these time points were not randomized to treatment. Treated volunteers continued receiving study medication >3 days and until cold symptoms resolved, as defined by 2 consecutive symptom scores <1, or until they had received treatment for 14 days. The duration of the cold was defined as the time from the start of study-medication administration to the first of the 2 consecutive symptom scores <1. In the subset of subjects studied at MUSC, nasal lavage was done each morning for the first 5 days after virus challenge, for detection of virus shedding and measurement of IL-8 concentration. The nasal lavage was done after the morning symptom assessment and before the first dose of study medication.
Subjects who presented to the study sites with a common-cold illness of <1 calendar day’s duration (effectively < 36 h), reported >2 different symptoms, and had a total symptom score of >2 were randomized to receive 1 of the treatments. As in the challenge study, all volunteers received medication >3 days and until cold symptoms resolved, as defined by 2 consecutive symptom scores <1, or until they had received treatment for 14 days. The duration of the cold was defined as the time from the start of study-medication administration to the first of the 2 consecutive symptom scores <1.

Results and discussion

Results:

Zinc gluconate treatment led to a significant reduction in the median duration of symptoms in volunteers with experimentally induced rhinovirus colds. This observation must be interpreted with caution, however, in light of the fact that zinc gluconate had no effect on the severity of symptoms during the first 3 days of treatment for induced colds and had no effect on either the duration or severity of natural colds. Zinc acetate lozenges had no effect on the duration or severity of symptoms in either the experimental or natural study model.

Applicant's summary and conclusion

Conclusions:

Zinc gluconate treatment led to a significant reduction in the median duration of symptoms in volunteers with experimentally induced rhinovirus colds. However, zinc gluconate had no effect on the severity of symptoms during the first 3 days of treatment for induced colds and had no effect on either the duration or severity of natural colds.
Zinc acetate lozenges had no effect on the duration or severity of symptoms in either the experimental or natural study model.

Executive summary:

Two clinical trials were conducted, one involving 273 subjects with experimental rhinovirus colds and the other involving 281 subjects with natural colds. Symptomatic volunteers were randomized to receive oral lozenges containing zinc gluconate (13.3 mg), zinc acetate (5 or 11.5 mg), or placebo. The median duration of illness in zinc gluconate recipients was 2.5 days, contrasted with 3.5 days in the placebo recipients, in the experimental colds study. Zinc gluconate had no effect on symptom severity and zinc acetate had no effect on either duration or severity. Neither formulation had an effect on the duration or severity of natural cold symptoms. Evaluation of blinding, taste, and adverse events revealed no significant differences among the 4 treatment arms.