Alpha Lipoic Acid in Geographic Atrophy | NCT02613572

ID	Type	Description	Link
822311	Other Identifier	University of Pennsylvania, Coordinating IRB
201604726	Other Identifier	University of Iowa, IRB

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
alpha lipoic acid (ALA) 600mg once daily x 5 days	Experimental	All 15 patients recruited to the Phase I part will take escalating doses of alpha lipoic acid (ALA) open label. Each enrolled subject will take 600 mg of oral ALA once daily with a meal for 5 days. If well-tolerated, each subject will then take 800 mg of oral ALA once daily with a meal for 5 additional days. If 800 mg of oral ALA is well-tolerated, then subjects will then take 1200 mg of oral ALA once daily with a meal for 5 days.	Drug: alpha lipoic acid
alpha lipoic acid 800mg	Experimental	once daily with meal x 5 days	Drug: alpha lipoic acid
alpha lipoic acid 1200mg	Experimental	once daily x 5 days	Drug: alpha lipoic acid
Placebo 600mg	Placebo Comparator	All 50 subjects in Phase II will be double blinded and randomized to either placebo or ALA. Each will take one 600mg capsule of ALA (or placebo) once daily with a meal for 2 weeks and then increase to two 600 mg capsules of ALA (or placebo) once daily with a meal for the	Drug: Placebo
ALA 600 mg	Experimental	once daily with a meal for 2 weeks

Name	Type	Description	Arm Group Labels	Other Names
alpha lipoic acid	Drug		ALA 1200mg ALA 600 mg alpha lipoic acid (ALA) 600mg once daily x 5 days alpha lipoic acid 1200mg alpha lipoic acid 800mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Phase I: Percentage of Participants With Adverse Events	The percent of adverse events that develop will be stratified by the alpha lipoic acid dose.	15 days
Phase II: Mean Annual Growth of Geographic Atrophy (Fundus Autofluorescence) - Total Area of Geographic Atrophy (mm2) - Unadjusted	The rate of change over time in area of Geographic Atrophy (GA) in the study eye. This is determined by masked grading of Fundus Autofluorescence by an image reading center, in participants randomized to placebo or 1200 mg once daily of ALA. The values represent the annualized change from baseline to 18 months. Mean annual geographic atrophy growth rate was calculated by taking the total atrophy area at 18 months minus the baseline area. This value was then divided by 18 months and then multiplied by 12 months to get the annual growth rate. Timepoints for the study were baseline, 0, 6, 12, and 18 months. The baseline and 18 month timepoints were used for the annualized calculations as noted below.	18 months
Phase II: Mean Annual Growth of Geographic Atrophy (Fundus Autofluorescence) - Total Area of GA (mm2) - Adjusted	The rate of change over time in area of Geographic Atrophy (GA) in the study eye. This is determined by masked grading of Fundus Autofluorescence by an image reading center, in participants randomized to placebo or 1200 mg once daily of ALA. The values represent the annualized change from baseline to 18 months. Mean annual geographic atrophy growth rate was calculated by taking the total atrophy area at 18 months minus the baseline area. This value was then divided by 18 months and then multiplied by 12 months to get the annual growth rate. Timepoints for the study were baseline, 0, 6, 12, and 18 months. The baseline and 18 month timepoints were used for the annualized calculations as noted below.	18 months
Phase II: Mean Annual Growth of Geographic Atrophy (Fundus Autofluorescence) - Square Root of Area of GA (mm) - Unadjusted	The rate of change over time in area of Geographic Atrophy (GA) in the study eye. This is determined by masked grading of Fundus Autofluorescence (FAF) by an image reading center, in participants randomized to placebo or 1200 mg once daily of ALA. The values represent the annualized change from baseline to 18 months. Mean annual geographic atrophy growth rate was calculated by taking the total atrophy area at 18 months minus the baseline area. This value was then divided by 18 months and then multiplied by 12 months to get the annual growth rate. For square root transformed data, the square root of area was used. Timepoints for the study were baseline, 0, 6, 12, and 18 months. The baseline and 18 month timepoints were used for the annualized calculations as noted below.

Secondary Outcomes

Measure	Description	Time Frame
Phase II: Mean Annual Change in Best-Corrected Visual Acuity (BCVA)	Unit of Measure. Mean annual change in best-corrected visual acuity was calculated by taking the letter score at 18 months minus the baseline letter score. This value was then divided by 18 months and then multiplied by 12 months to get the mean annual change in visual acuity. Timepoints for the study were baseline, 0, 6, 12, and 18 months. The baseline and 18 month timepoints were used for the annualized calculations as noted below.

Eligibility Module

Eligibility Criteria

Phase I

Inclusion Criteria:

Ages 65-90
Female participants must be menopausal. Male participants are required to use contraception.
Able to give informed consent
For the study duration (15 days), the subject must remain in the country, remain within 4 hours of travel time (by car or airplane), have access to medical care if needed, and provide contact information so the subject can be reached as needed.

Exclusion Criteria:

Blood Pressure greater than 190/100 at the baseline visit
Pulse greater than 100 at the baseline visit
Acute and ongoing systemic infection
History of dementia
Participant has a condition that, in the opinion of the investigator, gives them an unstable medical status.
Participant has geographic atrophy and the investigator believes the participant is a candidate for enrollment into the planned Phase 2 trial for geographic atrophy.

Phase II

Inclusion Criteria

Age 55-90
Diagnosis of geographic atrophy from age-related macular degeneration in the study eye. The largest geographic atrophy (GA) lesion must be a minimum of 0.5 optic disk area (DA) (1.25 mm2) and no more than 6 DA in size (15.0 mm2). GA is defined as one or more well-defined, usually more or less circular patches of loss of the retinal pigment epithelium (RPE), typically with exposure of underlying choroidal blood vessels. If the GA is multifocal and the largest lesion is < 0.5 DA, then there should be at least 3 lesions ≥ 250 microns in greatest linear diameter.
Best-Corrected Visual Acuity (BCVA) between 20/20 and 20/400 in the study eye.
Female participants must be menopausal. Male participants are required to use contraception and cannot donate sperm during study participation.
Presence of hyperfluorescence at the edge of GA on autofluorescence imaging.
Ability to give informed consent.
If a subject has two eligible eyes, then both eyes can be enrolled into the study.
Subject must have mailed back the medication bottle after the 10 day run-in phase, demonstrating that they have taken ≥ 80% of the capsules.

Exclusion Criteria

Evidence of ocular disease other than AMD in the study eye that may confound the study outcomes (e.g., History of myopic degeneration, choroidal neovascularization, central serous chorioretinopathy, severe diabetic retinopathy, uveitis, vitelliform dystrophy, or macular edema).
Presence of geographic atrophy that is already touching clearly defined beta peripapillary atrophy or is already touching the optic disc. Beta peripapillary atrophy is defined as peripapillary atrophy in which either the sclera or choroidal vessels are clearly visible.
Any history of intravitreal injection in the study eye for AMD or choroidal neovascularization.

However, if a subject develops choroidal neovascularization in the study eye during the study, then the subject will receive the standard of care intravitreal injection treatments per the investigator. The subject will continue to stay in the study. Treatment of choroidal neovascularization (CNV) or other diseases in the non-study eye is at the investigator's discretion.

History of intravitreal injection of any agent (e.g., triamcinolone) other than anti-VEGF (vascular endothelial growth factor) in the study eye within the last four months prior to study enrollment.
History of laser treatment (including photodynamic therapy) to the macula for the study eye.
History of intraocular surgery within 90 days. for the study eye.
History of anterior segment laser (laser peripheral iridotomy, laser to trabecular meshwork, YAG capsulotomy) within 90 days for the study eye.
Media opacity (corneal scar, cataract) that would prevent adequate fundus imaging for the study eye.
Any history of participation in another therapeutic clinical trial for GA.
Participation currently or within the past 30 days in another therapeutic clinical trial in which a systemic or ocular study medication is received by the subject.
GA in the study eye due to a cause other than AMD
History of prior use of ALA.
AREDS (Age Related Eye Disease Study) vitamins taken at standard doses are not considered an exclusion criterion. Taking a standard multivitamin is not considered an exclusion criterion. However, the multivitamin should not contain alpha lipoic acid (also known as thioctic acid).
Taking antioxidant supplements other than a standard multivitamin (such as bilberry, vitamin C that is not part of a multivitamin or taken at higher doses than the AREDS formula, vitamin E that is not part of a multivitamin or taken at higher doses than the AREDS formula, or other similar antioxidants) within one month of enrollment is an exclusion criteria; these patients should discontinue the antioxidant supplement one month before enrollment in order to participate. Taking a supplement that has antioxidant potential that is recommended by a physician as standard-of-care medical management is not an exclusion criterion.).
Participant has a condition that, in the opinion of the investigator, would preclude participation in the study for 18 months (e.g., unstable medical status including blood pressure and glycemic control, unstable psychiatric history, moving and not able to return for all planned study visits).
History of a formal diagnosis of dementia by a neurologist.
History of gastric ulcer within the past 5 years.
History of irritable bowel syndrome within the past 5 years.

Name	Affiliation	Role
Benjamin J Kim, MD	University of Pennsylvania	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of Iowa Hospitals and Clinics, Department of Ophthalmology & Visual Sciences		Iowa City	Iowa	52242	United States

PubMed Identifier	Type	Citation	Retractions
27729766	Background	Sarezky D, Raquib AR, Dunaief JL, Kim BJ. Tolerability in the elderly population of high-dose alpha lipoic acid: a potential antioxidant therapy for the eye. Clin Ophthalmol. 2016 Sep 29;10:1899-1903. doi: 10.2147/OPTH.S115900. eCollection 2016.

Arm/Group Information

ID	Title	Description
FG000	Alpha Lipoic Acid (ALA) 600, 800, 1200 mg	Phase I: All subjects recruited to the Phase I part will take escalating doses of alpha lipoic acid (ALA) open label. Each enrolled subject will take 600 mg of oral ALA once daily with a meal for 5 days. If well-tolerated, each subject will then take 800 mg of oral ALA once daily with a meal for 5 additional days. If 800 mg of oral ALA is well-tolerated, then subjects will then take 1200 mg of oral ALA once daily with a meal for 5 days.
FG001	Placebo 1200mg	Phase II: All subjects in Phase II will be double blinded and randomized to either placebo or ALA. Each will take one 600 mg capsule of ALA (or placebo) once daily with a meal for 2 weeks and then increase to two 600 mg capsules of ALA (or placebo) once daily with a meal for the entire remainder of the 18 month period of the study.
FG002	Alpha Lipoic Acid (ALA) 1200mg	Phase II: All subjects in Phase II will be double blinded and randomized to either placebo or ALA. Each will take one 600 mg capsule of ALA (or placebo) once daily with a meal for 2 weeks and then increase to two 600 mg capsules of ALA (or placebo) once daily with a meal for the entire remainder of the 18 month period of the study.

ID	Title	Description
BG000	Alpha Lipoic Acid (ALA) 600, 800 &1200 mg	Phase I: All subjects recruited to the Phase I part will take escalating doses of alpha lipoic acid (ALA) open label. Each enrolled subject will take 600 mg of oral ALA once daily with a meal for 5 days. If well-tolerated, each subject will then take 800 mg of oral ALA once daily with a meal for 5 additional days. If 800 mg of oral ALA is well-tolerated, then subjects will then take 1200 mg of oral ALA once daily with a meal for 5 days.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Phase I: Percentage of Participants With Adverse Events

The percent of adverse events that develop will be stratified by the alpha lipoic acid dose.

Phase I: 15 subjects took escalating ALA doses (600mg, 800mg, 1200mg). 1 subject withdrew after 800mg due to wanting to delay start of 1200mg dose beyond planned completion date.

Posted

Count of Participants

Participants

15 days

ID	Title	Description
OG000	Alpha Lipoic Acid (ALA) 600 mg	Phase I: All subjects recruited to the Phase I part will take escalating doses of alpha lipoic acid (ALA) open label. Each enrolled subject will take 600 mg of oral ALA once daily with a meal for 5 days. If well-tolerated, each subject will then take 800 mg of oral ALA once daily with a meal for 5 additional days. If 800 mg of oral ALA is well-tolerated, then subjects will then take 1200 mg of oral ALA once daily with a meal for 5 days.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Alpha Lipoic Acid (ALA) 600 mg	Phase I: All subjects recruited to the Phase I part will take escalating doses of alpha lipoic acid (ALA) open label. Each enrolled subject will take 600 mg of oral ALA once daily with a meal for 5 days. If well-tolerated, each subject will then take 800 mg of oral ALA once daily with a meal for 5 additional days. If 800 mg of oral ALA is well-tolerated, then subjects will then take 1200 mg of oral ALA once daily with a meal for 5 days.

ID	Term
D012162	Retinal Degeneration
D012164	Retinal Diseases
D005128	Eye Diseases

ID	Term
D002264	Carboxylic Acids
D009930	Organic Chemicals
D013876	Thiophenes
D013457	Sulfur Compounds