No registrations found.
ID
Source
Health condition
AMD, complement, zinc
Sponsors and support
P.O. Box 9101, 6500 HB Nijmegen
The Netherlands
Radboud University Nijmegen Medical Centre
Intervention
Outcome measures
Primary outcome
The primary outcome is the serum level of activation fragment C3d and complement component C3. The C3d/C3 ratio will be calculated. This ratio is the activity marker of the alternative complement pathway.
Secondary outcome
The secondary outcome is the correlation between this supposed drop in serum level C3 en C3d and Y402H polymorphism status in CFH.
Background summary
Rationale:
Zinc and antioxidants supplementation can delay the
progression of age-related macular degeneration (AMD). 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.
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 and ARMS2 polymorphism,
enabling us to identify subgroups of patients more susceptible to the
beneficiary effect of zinc.
Study design:
80 AMD patients 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.
Study population:
80 AMD patients of 50 years of age or older with
extensive small, intermediate, and large drusen, geographic atrophy
and/or exudative AMD but without active disease as demonstrated by
active neovascularisation, will be recruited for the study.
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.
The reason for the presence of a small amount of copper is based on the
fact that zinc and copper compete for the same membrane transport
systems. The ratio zinc to copper in the present preparation reflects
the physiological situation. The same reasoning has also been followed
in the Age-Related Eye Disease Study (AREDS) of the National Institutes
of Health in the US.
Study objective
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.
Study design
Serum level of complement component C3 and activation
fragments C3d will be analyzed prior, during and post treatment.
Intervention
All participants of the study will receive oral 50 mg zinc as zinc sulfate and 1 mg copper as cupric sulphate dailly for 3 months.
Inclusion criteria
1. Men and women ≥ 50 years of age;
2. AMD patients previously included in the EUGENDA database;
3. Previously genotyped for Y402H (rs1061170) gene variation (from EUGENDA database);
4. 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;
5. Informed consent.
Exclusion criteria
1. Active leakage from CNV due to AMD;
2. Ongoing anti/VEGF treatment;
3. Ongoing infection;
4. Subretinal hemorrhages;
5. History of any vitreous hemorrage within 12 weeks;
6. Other ocular disorders that may confound the interpretation of the study results;
7. Systemic or local steroid treatment within the last three months;
8. Use of any antibiotica;
9. Prolonged use of diuretics;
10. Supplemental use of iron (38-65 mg/day of elemental iron);
11. Use of zink and vitamin supplements one month prior to the study;
12. Systemic 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
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL2488 |
| NTR-old | NTR2605 |
| CCMO | NL31655.091.10 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |
| OMON | NL-OMON35087 |