Dark Adaptation as an Early Indicator of Response to Statin Therapy for Intermediate AMD (DELPHI)

interventional trial for off label use of high dose atorvastatin 80 mg in intermediate AMD patients and correlate recovery response measured by dark adaptation recovery time with drusen volume reduction measured by SD-OCT

Study Overview

• Status: Recruiting
• Conditions: Age-related Macular Degeneration
• Intervention / Treatment: Drug: Atorvastatin 80mg

Detailed Description

Dark adaptation recovery time is a sensitive marker of AMD progression in intermediate AMD, largely owing to drusen volume providing a transport barrier that slows the transfer of nutrients between the choroid and photoreceptors2. Consequently, dark adaptation may provide an early indication of response vs. nonresponse, aiding case-by-case decisions on continuation of treatment when patients experience adverse side effects (e.g., elevated CPK or liver enzymes) or when atorvastatin provides insufficient lipid control in patients also at high-risk for cardiovascular disease (and switching to an alternative statin might be desirable).

• Study Type: Interventional
• Enrollment (Anticipated): 21
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: John B Miller, MD; Phone Number: 617-573-3750; Email: John_Miller@meei.harvard.edu
• Study Contact Backup: Name: Deeba Husain; Phone Number: 617-573-3750; Email: Deeba_Husain@meei.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts Eye and Ear Infirmary
      • Contact: John B Miller, MD; Phone Number: 617-573-3750; Email: John_Miller@meei.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All subjects with intermediate AMD diagnosis in one or both eyes will be considered, regardless the severity stage and subtype of disease in the other eye.

High-risk iAMD (numerous large, confluent drusen covering ≥ 0.5 disk area, with or without pigmentary changes but having no evidence of GA or CNV) in the study eye

Subjects can have either:

(i) Bilateral high-risk iAMD, or (ii) High-risk iAMD in one eye with GA and/or CNV in the fellow eye.

Exclusion Criteria:

• Patient previously taking high dose Atorvastatin 80 mg
• Patients previously taking other statins than high dose atorvastatin, in whom primary care provider (PCP) feels cannot be safely moved to high dose atorvastatin or those in which high dose atorvastatin is deemed contraindicated by PCP
• Patients with known adverse reaction to statins
• Patients with severe renal disease or multiple comorbidities
• Age >85 years
• Pregnancy
• Patients with concomitant use of cyclosporine
• Active uveitis;
• Ocular infection;
• Any retinopathy other than AMD;
• Media opacities;
• Refractive error equal or superior to 6 diopters (spherical equivalent);
• Any previous retina surgery;
• Other ocular surgery or intra-ocular procedure in the study eye (injection other than anti angiogenic injection, laser) within the 90 days prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Intermediate Age-Related macular degeneration patients; Subjects can have either: Bilateral high-risk iAMD; High-risk iAMD in one eye with GA and/or CNV in the fellow eye No control arm	Drug: Atorvastatin 80mg; Patient will be receiving 80mg of Atorvastatin, if they are able to tolerate it from the start to the end of the study.; Other Names: Lipitor 80 mg(Brand name)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Dark Adaptation recovery time measured by change in Rod Intercept time (RIT)	Determine weather improvement in dark adaptation recovery time or rod intercept time (RIT) can be used as an early indicator of positive response to high dose statin therapy for intermediate AMD patients	18 Months
Change in drusen volume measured by Spectral Domain OCT	To measure and quantify improvement or positive response to high dose statin therapy in patients with intermediate AMD using drusen volume measured by SDOCT	18 months
To correlate visual functions of dark adaption with change in drusen volume	Patient will have Dark Adaptation testing performed to check change in vision function with changes in drusen volume.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To correlate Best Corrected Visual Acuity and retinal structural evaluation of study patients	Patient will have Best Corrected visual acuity, testing performed to check changes in vision function	18 months
To correlate change in contrast sensitivity and retinal structural evaluation of study patients	Patient will have quantitative contrast sensitivity function testing performed to check change in vision function with changes in drusen volume.	18 months
To correlate change in microperimetry visual functional and retinal structural evaluation of study patients	Patient will have microperimetry function testing performed to check change in this vision function with changes in drusen volume	18 months

Collaborators and Investigators

• Sponsor: Massachusetts Eye and Ear Infirmary
• Investigators: Principal Investigator: John B Miller, MD, Massachusetts Eye and Ear Infirmary, Harvard Medical School

Publications and helpful links

General Publications

• Vavvas DG, Daniels AB, Kapsala ZG, Goldfarb JW, Ganotakis E, Loewenstein JI, Young LH, Gragoudas ES, Eliott D, Kim IK, Tsilimbaris MK, Miller JW. Regression of Some High-risk Features of Age-related Macular Degeneration (AMD) in Patients Receiving Intensive Statin Treatment. EBioMedicine. 2016 Feb 4;5:198-203. doi: 10.1016/j.ebiom.2016.01.033. eCollection 2016 Mar.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: January 30, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Actual): October 14, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: 2020P001265

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes