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Herbal Medication to Treat Dry Eye in Peri/ Post-menopausal Women

Primary Purpose

Dry Eye

Status
Recruiting
Phase
Early Phase 1
Locations
Singapore
Study Type
Interventional
Intervention
Wei's Qi Ju Gan Lu Formula
Placebo
Sponsored by
Singapore National Eye Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dry Eye focused on measuring Menopausal women, Herbal treatment, Quality of Life, eicosanoids, cytokines

Eligibility Criteria

40 Years - 79 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  1. Age 40-79 years old women
  2. Peri and Post-menopausal women
  3. Chief complaint of participant should be consistent with dry eye symptoms based on SPEED Questionnaire, with a score of > 6 (Appendix 5)
  4. History of presenting TCM score symptoms:

    4.1. TCM dry eye assessment score (Appendix 3) The pattern deviation can be determined if 3 or more main symptoms are present (one of which is a localized eye symptom and one of which is a system symptom), together with at least one accompanying symptom.

    4.2 Liver-Kidney yin deficiency assessment score (Appendix 4) This form is to determine the extent of Liver-Kidney Yin Deficiency (assessed at SCHMI).

    Any score<14 will not satisfy the criterion for Liver Kidney Yin Deficiency and will not be recruited. This detailed TCM score will also be a secondary outcome measure in the analysis of pre/post herbal treatment (see below).

  5. Clinical signs:

    5.1. Tear break up time (TBUT) ≤10s or Schirmer I test ≤10mm/5 mins

  6. Normal renal and liver function at baseline, i.e., all parameters within the reference value

Exclusion Criteria:

  1. Currently or intention to use hormonal therapy (eg. cancer patients who is on tamoxifen)
  2. Currently pregnant or breastfeeding
  3. Hysterectomy procedure done previously
  4. Removal of cysts or polyp procedure done previously
  5. Requirement to wear contact lens, and having worn such lenses in week preceding eligibility
  6. Glaucoma, significant cataract, age related macular degeneration or other ophthalmic disease, eg. Extraocular muscle palsies, facial paralysis, ectropion, entropion, trichiasis
  7. Requirement of any eyedrops other than artificial tears.
  8. Previous eye surgeries including LASIK (within 6 months) or punctal plugs in-situ
  9. Autoimmune systemic diseases: Steven-Johnson syndrome, Sjogren's syndrome, Rheumatoid Arthritis, Lupus
  10. Systemic disease requiring regular medication (except hypertension and lipidemia)

Sites / Locations

  • Singapore National Eye CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active herbal capsules

Placebo capsules

Arm Description

Wei's Qi Ju Gan Lu Formula is a herbal formulation initiated by the senior TCM collaborator, Prof Wei QP. This TCM formulation is prescribed to treat the dry eye patients with "liver-kidney yin deficiency". The treatment regulation aims to nourish the Liver and Kidney, enrich yin deficiency, in order to promote tears production, hence treatment of Dry Eye.

Placebo capsule which contains 0.5g maltodextrin without any herbs medicine.

Outcomes

Primary Outcome Measures

Change in SPEED score
To assess the improvement of dry eye symptoms by SPEED questionnaire. 0 score is the minimum (no dry eye symptom); 64 is the maximum score (most symptomatic)

Secondary Outcome Measures

Change in SPEED score
To assess the improvement of dry eye symptoms by SPEED questionnaire. 0 score is the minimum (no dry eye symptom); 64 is the maximum score (most symptomatic)
Change in Sleep score
To assess the improvement of sleep score. 0 score is the minimum (no sleeping issue); 24 score is the maximum (high risk of Epworth Sleepiness Scale)
Change in Depression score
To assess the improvement in depression score. 0 score is the minimum (no sign of depression); 48 score is the maximum (very likely to have depression)
Change in TCM score (Liver-Kidney Yin Deficiency)
To assess the change in TCM score. Liver-Kidney Yin deficiency is within the range from 14-30. (score <14 not diagnosed as Liver-Kidney Yin Deficiency); (score 14-20 Liver-Kidney Yin deficiency Type I- Level 1 mild); (score 21-30 Liver-Kidney Yin deficiency Type II- Level 2 moderate); (score >30 Liver-Kidney Yin deficiency Type III- Level 3 severe)

Full Information

First Posted
March 22, 2022
Last Updated
April 10, 2023
Sponsor
Singapore National Eye Centre
Collaborators
Singapore Chung Hwa Medical Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05319041
Brief Title
Herbal Medication to Treat Dry Eye in Peri/ Post-menopausal Women
Official Title
Randomised Placebo Controlled Study of Herbal Medication to Treat Dry Eye in Peri/ Post-menopausal Women
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 11, 2022 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Singapore National Eye Centre
Collaborators
Singapore Chung Hwa Medical Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Dry eye disease (DED) in less severe forms are very common, and should ideally be treated outside hospitals, eg., through primary care services and exploiting holistic therapies such as traditional medicine. This will keep the care affordable and accessible despite a large burden of care. Postmenopausal women, compared to others in the population, have a higher incidence of DED. Large-scale epidemiological studies done in the United States have shown that the rate of DED in women over 50 years old is nearly double that in men over 50, at 7% and 4%, respectively. Studies have demonstrated that there is a hormonal etiology behind this group's susceptibility to DED, although the precise hormonal imbalance and mechanistic pathway for DED are still unclear. A significant number of women seen at the dry eye clinic are post-menopausal, and very symptomatic, though many do not have the corneal epitheliopathy evidenced by dye staining. Such patients are not likely to benefit from conventional prescription drugs for dry eye, such as cyclosporine and corticosteroids. Hormonal replacement therapy for menopausal women has not been universally accepted, and there may be an increased risk of carcinomas, on the other hand, topical hormonal therapy for dry eye is not widely available, and still controversial, so there is a definite unmet need for new therapeutic modalities to treat dry eye in post-menopausal women. Traditional Chinese Medicine (TCM) is a form of complementary medicine that aims to treat yin or yang deficiency syndromes, using modalities like herbs, acupuncture or moxibustion. Menopause in women, particularly in Asia, has been linked to yin-deficiency, in one study, 73% of Chinese post-menopausal women suffered from kidney yin-deficiency. A review of randomized controlled trials of TCM treatment showed that certain modalities like soy and phytoestrogens have been useful in the treatment of syndromes in menopause, such as hot flushes.
Detailed Description
The overall hypothesis is that the Traditional Chinese Medicine (TCM) modality of a specific herbal formulation can improve the symptoms and signs of post-menopausal dry eye in women, and objectively, these improvements are associated with improvement of dry eye symptoms, and alteration of levels of tear eicosanoids or cytokines. TCM in the treatment of dry eye A meta-analysis of TCM in treatment of Sjogren's syndrome showed that TCM is promising but there were some flaws in the studies reviewed. Jiang et al, in particular has found that mistletoe, in combination with carboxymethylcellulose eyedrops were effective in reducing dry eye symptoms and signs, compared to normal saline eyedrops, in post-menopausal women.Unfortunately, the authors did not compare the effect of this combination with carboxymetholycellulose eyedrops, a commonly used artificial tear, per se. In postmenopausal women, dry eye is not only more common, but the symptoms may be confused/related to mood changes like depression and anxiety, and sleep disorders, all of which were linked to the post-menopausal state, where there may be yin deficiency. Recently the investigators found acupuncture to be useful in the treatment of elderly people with lung-kidney yin-deficiency type of dry eye in Singapore. In addition, TCM Practitioners in Singapore were interested in the treatment of dry eye. However, no study has evaluated the use of TCM herbs in peri-menopausal patients with dry eye in robust way. Previous studies by the senior TCM collaborator, Prof Wei QP has concluded that steaming treatment by (Wei's Qi Ju Gan Lu Formula) combined with sodium hyaluronate eye drops could improve the objective indexes like TBUT and corneal staining as well as subjective symptoms in peri-menopausal patients with aqueous tear deficiency dry eye of liver and kidney deficiency. Prof Wei has also studied treatment of dry eye through oral medication (with the method of strengthening the water element to nourish wood element under the TCM perspective) combined with artificial tears, and concluded that the prescription can effectively treat dry eyes by promoting the tear secretion and prolonging BUT. Recently, the investigators have also discovered that herbal medication have a trend to lower the tear levels of inflammatory proteins (journal under review). Hence, this current study intends to follow-up with the effectiveness of oral medication of (Wei's Qi Ju Gan Lu Formula) for patients suffering from peri/ post-menopausal dry eye disease of the "Liver-Kidney yin deficiency" pattern differentiation. 1.1.1 Rationale for the Study Purpose Clinical significance Traditional Chinese Medicine (TCM), when combined with psychotherapy, has been shown to be effective in targeting yin-deficiency in the treatment of menopause, although the effect of such treatment on dry eye symptoms has not been specifically investigated. If TCM is effective in the treatment of post-menopausal women, it can be implemented at the primary care level, so relieving the specialist centers of this type of patients, thereby saving health-care costs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye
Keywords
Menopausal women, Herbal treatment, Quality of Life, eicosanoids, cytokines

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active herbal capsules
Arm Type
Experimental
Arm Description
Wei's Qi Ju Gan Lu Formula is a herbal formulation initiated by the senior TCM collaborator, Prof Wei QP. This TCM formulation is prescribed to treat the dry eye patients with "liver-kidney yin deficiency". The treatment regulation aims to nourish the Liver and Kidney, enrich yin deficiency, in order to promote tears production, hence treatment of Dry Eye.
Arm Title
Placebo capsules
Arm Type
Placebo Comparator
Arm Description
Placebo capsule which contains 0.5g maltodextrin without any herbs medicine.
Intervention Type
Drug
Intervention Name(s)
Wei's Qi Ju Gan Lu Formula
Intervention Description
The formulation, Wei's Qi Ju Gan Lu Formula, is initiated by the senior TCM collaborator, Prof Wei QP, is formulated to treat the dry eye patients with "liver-kidney yin deficiency". The treatment regulation aims to nourish the Liver and Kidney, enrich yin deficiency, in order to promote tears production, hence treatment of Dry Eye.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
0.5g maltodextrin without any herbs medicine
Intervention Description
0.5g maltodextrin without any herbs medicine
Primary Outcome Measure Information:
Title
Change in SPEED score
Description
To assess the improvement of dry eye symptoms by SPEED questionnaire. 0 score is the minimum (no dry eye symptom); 64 is the maximum score (most symptomatic)
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Change in SPEED score
Description
To assess the improvement of dry eye symptoms by SPEED questionnaire. 0 score is the minimum (no dry eye symptom); 64 is the maximum score (most symptomatic)
Time Frame
4 months
Title
Change in Sleep score
Description
To assess the improvement of sleep score. 0 score is the minimum (no sleeping issue); 24 score is the maximum (high risk of Epworth Sleepiness Scale)
Time Frame
3 months
Title
Change in Depression score
Description
To assess the improvement in depression score. 0 score is the minimum (no sign of depression); 48 score is the maximum (very likely to have depression)
Time Frame
3 months
Title
Change in TCM score (Liver-Kidney Yin Deficiency)
Description
To assess the change in TCM score. Liver-Kidney Yin deficiency is within the range from 14-30. (score <14 not diagnosed as Liver-Kidney Yin Deficiency); (score 14-20 Liver-Kidney Yin deficiency Type I- Level 1 mild); (score 21-30 Liver-Kidney Yin deficiency Type II- Level 2 moderate); (score >30 Liver-Kidney Yin deficiency Type III- Level 3 severe)
Time Frame
3 months

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Peri and Post-menopausal women age between 40-79 years old
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age 40-79 years old women Peri and Post-menopausal women Chief complaint of participant should be consistent with dry eye symptoms based on SPEED Questionnaire, with a score of > 6 (Appendix 5) History of presenting TCM score symptoms: 4.1. TCM dry eye assessment score (Appendix 3) The pattern deviation can be determined if 3 or more main symptoms are present (one of which is a localized eye symptom and one of which is a system symptom), together with at least one accompanying symptom. 4.2 Liver-Kidney yin deficiency assessment score (Appendix 4) This form is to determine the extent of Liver-Kidney Yin Deficiency (assessed at SCHMI). Any score<14 will not satisfy the criterion for Liver Kidney Yin Deficiency and will not be recruited. This detailed TCM score will also be a secondary outcome measure in the analysis of pre/post herbal treatment (see below). Clinical signs: 5.1. Tear break up time (TBUT) ≤10s or Schirmer I test ≤10mm/5 mins Normal renal and liver function at baseline, i.e., all parameters within the reference value Exclusion Criteria: Currently or intention to use hormonal therapy (eg. cancer patients who is on tamoxifen) Currently pregnant or breastfeeding Hysterectomy procedure done previously Removal of cysts or polyp procedure done previously Requirement to wear contact lens, and having worn such lenses in week preceding eligibility Glaucoma, significant cataract, age related macular degeneration or other ophthalmic disease, eg. Extraocular muscle palsies, facial paralysis, ectropion, entropion, trichiasis Requirement of any eyedrops other than artificial tears. Previous eye surgeries including LASIK (within 6 months) or punctal plugs in-situ Autoimmune systemic diseases: Steven-Johnson syndrome, Sjogren's syndrome, Rheumatoid Arthritis, Lupus Systemic disease requiring regular medication (except hypertension and lipidemia)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cynthia Boo, BsC
Phone
98206648
Email
cynthia.boo.s.k@singhealth.com.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Louis Tong, PhD
Organizational Affiliation
Singapore National Eye Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Singapore National Eye Centre
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Louis Tong, PhD
Email
louis.tong.h.t@singhealth.com.sg

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Herbal Medication to Treat Dry Eye in Peri/ Post-menopausal Women

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