Alpha Lipoic Acid in Geographic Atrophy

NCT02613572 | Completed Phase 1 Results DMC

• 3 other identifiers: 822310822311201604726
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 5

Brief Summary

Because of its iron-chelating and antioxidant properties, alpha lipoic acid may be a treatment for geographic atrophy (GA) secondary to age-related macular degeneration. There is ample published data about the safety and pharmacokinetics of alpha lipoic acid in adults. However, there is not much data on the safety and tolerability of higher doses of alpha lipoic acid in the elderly population. The purpose of Phase I of this protocol is to determine if there are safety/tolerability concerns seen when higher doses of alpha lipoic acid are taken by subjects 65 years of age or older. The objective of Phase 2 of this protocol is to determine the effects of ALA on the progression of GA in subjects with AMD. The central hypothesis, based on the existing literature, is that oral ALA reduces the rate of enlargement of GA in AMD subjects. The rationale is that the antioxidant and iron chelating effects of ALA will slow down one of the major pathways responsible for GA progression.

Conditions

Age-Related Macular Degeneration

Outcome Measures

Primary Outcomes (5)

• 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.

  18 months

• Phase II: Mean Annual Growth of Geographic Atrophy (Fundus Autofluorescence) - Square Root of Area of GA (mm) - 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 (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.

  18 months

Secondary Outcomes (1)

• Phase II: Mean Annual Change in Best-Corrected Visual Acuity (BCVA)

  18 months

Study Arms (7)

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

Drug: alpha lipoic acid

Placebo 1200mg

PLACEBO COMPARATOR

Two 600mg capsules once daily with a meal for the entire remainder of the 18 month period of the study

Drug: Placebo

ALA 1200mg

EXPERIMENTAL

Two 600mg capsules once daily with a meal for the entire remainder of the 18 month period of the study

Drug: alpha lipoic acid

Interventions

alpha lipoic acid DRUG

Also known as: thioctic acid

ALA 1200mg; ALA 600 mg; alpha lipoic acid (ALA) 600mg once daily x 5 days; alpha lipoic acid 1200mg; alpha lipoic acid 800mg

Placebo DRUG

Placebo 1200mg; Placebo 600mg

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (5)

University of Iowa Hospitals and Clinics, Department of Ophthalmology & Visual Sciences

Iowa City, Iowa, 52242, United States

Location

NJ Retina

Teaneck, New Jersey, 07666, United States

Location

Oregon Regina. LLP

Eugene, Oregon, 97401, United States

Location

Retina Northwest, P.C.

Portland, Oregon, 97210, United States

Location

Scheie Eye Institute of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 27729766 BACKGROUND

MeSH Terms

Conditions

Macular Degeneration

Interventions

Thioctic Acid

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Carboxylic Acids; Organic Chemicals; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids

Results Point of Contact

• Title: Benjamin J. Kim, MD
• Organization: Scheie Eye Institute; Perelman School of Medicine; University of Pennsylvania

benjamin.kim@uphs.upenn.edu

215-662-8675

Study Officials

• Benjamin J Kim, MD

  University of Pennsylvania

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2015
• First Posted: November 24, 2015
• Study Start: November 1, 2015
• Primary Completion: February 15, 2019
• Study Completion: March 1, 2019
• Last Updated: August 6, 2020
• Results First Posted: August 6, 2020

Record last verified: 2020-07

Locations

US (5)