1. To determine if zinc supplementation in AMD patients has a direct measurable effect on the complement system explaining the mechanism through which this substance exerts its influence on AMD progression.2. To determine whether this proposed…
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
- Immune disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the serum level of activation fragment C3d and
complement component C3, C3d/C3 ratio will be calculated. This ratio is the
activity marker of alternative complement pathway.
Secondary outcome
The secondary outcome is the correlation between this supposed drop in serum
level C3d and Y402H polymorphism status in CFH.
Background summary
Zinc and antioxidants supplementation can delay the progression of age-related
macular degeneration (AMD). The strongest genetic association for development
of AMD has been found with the complement factor H (CFH) gene, which encodes a
regulator of an innate immune system, the complement cascade. Compared to
controls, AMD patients have a higher level of complement-mediated inflammation
as demonstrated by subretinal complement deposits (drusen). The AREDS study has
demonstrated that zinc supplementation may prevent the progression of AMD and
preserve visual function in 21% of patients. In addition, it has been
demonstrated that zinc has the ability to temper activation of the complement
cascade by direct binding to active complement molecules.
Study objective
1. To determine if zinc supplementation in AMD patients has a direct measurable
effect on the complement system explaining the
mechanism through which this substance exerts its
influence on AMD progression.
2. To determine whether this proposed effect of zinc is influenced by the
genetic status, regarding the Y402H polymorphism in CFH,
enabling us to identify subgroups of patients more
susceptible to the beneficiary effect of zinc.
Study design
51 AMD patients, 17 heterozygous and 17 homozygous carriers of the risk CFH
genotype (CT and CC) as well as 17 homozygous nonrisk (TT) genotype will be
enrolled. These groups will receive 50 mg oral zinc supplements during 3
months. Serum level of complement component C3 and activation fragments C3d
will be analyzed prior, during and post treatment. In case the zinc
supplementation in AMD patients has a positive effect on complement parameters,
we will like to obtain one venous blood extraction, approximately two months
after the ending of the zinc.
Intervention
All participants of the study will receive daily oral 50 mg zinc as zinc
sulfate and 1 mg copper as cupric sulphate for 3 months.
Study burden and risks
All participants of this 5 month study will be preselected from EUGENDA, a
multi centre database for clinical and molecular analysis of age-related
macular degeneration. At the first visit, after signing informed consent forms,
each patient will undergo a routine ophthalmological examination, a
determination of best corrected visual acuity using ETDRS charts. Furthermore,
all patients will be examined by non invasive SD-OCT retina imaging. Zinc
supplement will be given during the period of 3 months. In order to measure and
monitor changes in serum complement levels at every visit (in total 4) venous
blood will be collected. In order to detect a symptoms that may indicate
ongoing infection at every visit the patient will undergo an interview
(approximately 5 minutes). In case the zinc supplementation in AMD patients has
a positive effect on complement parameters, approximately two months after the
ending of the zinc one more venous blood extraction (in total 5) and 5 min.
interview will be obtained.
Philips van Leydenlaan 15
6525 EX Nijmegen
Nederland
Philips van Leydenlaan 15
6525 EX Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
• Men and women >= 50 years of age.
• AMD patients previously included in the EUGENDA database.
• Previously genotyped for Y402H (rs1061170) gene variation (from EUGENDA
database).
• Patients with extensive small drusen, intermediate drusen, large drusen, advanced
neovascular AMD without neovascular activity in one or both eyes or geographic
atropy in one or both eyes.
• Informed consent.
Exclusion criteria
• Active leakage from CNV due to AMD.
• Ongoing anti/VEGF treatment.
• Ongoing infection.
• Subretinal hemorrhages.
• History of any vitreous hemorrage within 12 weeks.
• Other ocular disorders that may confound the interpretation of the study results.
• Systemic or local steroid treatment within the last three months.
• Use of any antibiotica.
• Prolonged use of diuretics.
• Supplemental use of iron (38-65 mg/day of elemental iron).
• Use of zink and vitamin supplements one month prior to the study.
• Systhemic diseases that may influence complement levels (atypical haemolytic
uraemic syndrome (aHUS), membranoproliferative glomerulonephritis type 2 (MG2)).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL31655.091.10 |
| OMON | NL-OMON22306 |