Lipoic Acid for Secondary Progressive Multiple Sclerosis (MS)

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01188811
• Collaborator: Oregon Health and Science University (Other)
• Enrollment: 54
• Location: 1
• Arms: 2
• Duration (Months): 58
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of the study is to determine if lipoic acid can protect the brain and slow disability in secondary progressive multiple sclerosis.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis, Chronic Progressive	Drug: lipoic acid; Drug: Placebo	Phase 2/Phase 3

Detailed Description

There are no approved medications that are neuroprotective or able to slow disability accumulation in secondary progressive multiple sclerosis (SPMS). This two-year study will determine if daily oral intake of lipoic acid, a natural supplement, will prove superior to placebo in reducing injury to the brain and reducing disability progression in SPMS. Neuroprotection will be measured by the extent of brain volume loss seen on MRI, and disability will be measured by neurological status and quality of life.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Lipoic Acid for Neuroprotection in Secondary Progressive MS
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: lipoic acid 28 subjects receive oral lipoic acid 1200mg daily	Drug: lipoic acid; 1200 mg taken by mouth daily starting on day one of the study and ending on the last day of study participation.; Other Names: alpha lipoic acid
Placebo Comparator: Arm 2: placebo 28 subjects receive placebo daily	Drug: Placebo; The placebo comparator will be taken by mouth daily starting on day one of the study and ending on the last day of study participation

Outcome Measures

Primary Outcome Measures

1. Brain Atrophy by MRI [% change brain volume from baseline to year 2]

Secondary Outcome Measures

1. Disability Measures: Mobility [Change in Timed 25 Foot Walk from baseline to year 2]

2. Safety Measure: Adverse Events [adverse events recorded from baseline to year 2]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of SPMS

• Age 40-70 years

• Able to understand English and able to give informed consent

Exclusion Criteria:

• Unable to undergo MRI testing

• For ambulatory subjects only, a self-reported medical or neurological condition other than MS that is a cause of progressive or fluctuating problems that affect walking(e.g. worsening neuropathy, uncontrolled lower extremity arthritis, uncontrolled heart or lung disease)

• For ambulatory subjects only, fixed and/or stable conditions of less than 1 years duration that affect walking (e.g. joint replacement, lumbar stenosis, alcoholism, stroke, etc.)

• Pregnant or breast-feeding.

• Current major disease or disorder other than MS (such as cancer, kidney, heart or lung disease, post-traumatic stress disorder) that may interfere with study procedures

• Natalizumab, mitoxantrone, azathioprine taken in the last 12 months

• Other immunosuppressants or chemotherapies taken in the last 12 months

• Scheduled (every 3 months or more frequently) IV steroids used in the last 12 months

• IV or oral steroids taken in the past 60 days.

• Lipoic acid taken in the past 60 days.

• Subject has insulin-dependent diabetes or is not controlled on oral diabetes medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Portland Health Care System, Portland, OR	Portland	Oregon	United States	97239

Sponsors and Collaborators

• VA Office of Research and Development
• Oregon Health and Science University

Investigators

• Principal Investigator: Rebecca Spain, MD MSPH, VA Portland Health Care System, Portland, OR

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01188811
• Other Study ID Numbers: B7493-W
• First Posted: Aug 26, 2010
• Last Update Posted: Feb 2, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by VA Office of Research and Development: Multiple Sclerosis; Multiple sclerosis, chronic progressive; Neuroprotective agents; Magnetic resonance imaging; Optical coherence tomography; Gait; Thioctic acid; Alpha-lipoic acid
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Thioctic Acid

Study Results

Participant Flow

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	28 subjects receive oral lipoic acid 1200mg daily lipoic acid: 1200 mg taken by mouth daily starting on day one of the study and ending on the last day of study participation.	28 subjects receive placebo daily Placebo: The placebo comparator will be taken by mouth daily starting on day one of the study and ending on the last day of study participation
Period Title: Overall Study
STARTED	28	26
COMPLETED	22	24
NOT COMPLETED	6	2

Baseline Characteristics

Arm/Group Title	Lipoic Acid	Placebo	Total
Arm/Group Description	28 subjects receive oral lipoic acid 1200mg daily lipoic acid: 1200 mg taken by mouth daily starting on day one of the study and ending on the last day of study participation.	28 subjects receive placebo daily Placebo: The placebo comparator will be taken by mouth daily starting on day one of the study and ending on the last day of study participation	Total of all reporting groups
Overall Participants	28	26	54
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	28 100%	26 100%	54 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.9 (6.7)	59.7 (6.1)	58.7 (6.4)
Gender (Count of Participants)
Female	16 57.1%	16 61.5%	32 59.3%
Male	12 42.9%	10 38.5%	22 40.7%
Region of Enrollment (participants) [Number]
United States	28 100%	26 100%	54 100%

Outcome Measures

1. Primary Outcome

Title	Brain Atrophy by MRI
Time Frame	% change brain volume from baseline to year 2

Outcome Measure Data

Analysis Population Description

22 subjects in the lipoic acid group and 24 in the placebo group completed the MRI outcome. Two outliers in the lipoic acid group were not included in analysis.

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	28 subjects receive oral lipoic acid 1200mg daily lipoic acid: 1200 mg taken by mouth daily starting on day one of the study and ending on the last day of study participation.	28 subjects receive placebo daily Placebo: The placebo comparator will be taken by mouth daily starting on day one of the study and ending on the last day of study participation
Measure Participants	20	24
Mean (Standard Deviation) [whole brain percent volume change]	-0.4 (0.7)	-1.3 (1.1)

2. Secondary Outcome

Title	Disability Measures: Mobility
Time Frame	Change in Timed 25 Foot Walk from baseline to year 2

Outcome Measure Data

Analysis Population Description

Outliers were removed and intention-to-treat analysis was performed on data from 21 participants in the lipoic acid group and 17 in the placebo group.

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	28 subjects receive oral lipoic acid 1200mg daily lipoic acid: 1200 mg taken by mouth daily starting on day one of the study and ending on the last day of study participation.	28 subjects receive placebo daily Placebo: The placebo comparator will be taken by mouth daily starting on day one of the study and ending on the last day of study participation
Measure Participants	21	17
Mean (Standard Deviation) [seconds]	-1.0 (2.8)	0.1 (2.0)

3. Secondary Outcome

Title	Safety Measure: Adverse Events
Time Frame	adverse events recorded from baseline to year 2

Outcome Measure Data

Analysis Population Description

Intention-to-treat analysis was performed on 27 participants in the lipoic acid group and 24 in the placebo group.

Arm/Group Title	Lipoic Acid	Placebo
Arm/Group Description	28 subjects receive oral lipoic acid 1200mg daily lipoic acid: 1200 mg taken by mouth daily starting on day one of the study and ending on the last day of study participation.	28 subjects receive placebo daily Placebo: The placebo comparator will be taken by mouth daily starting on day one of the study and ending on the last day of study participation
Measure Participants	27	24
Total number adverse events	81	69
Total number serious adverse events	9	6

Adverse Events

Arm/Group Title	Lipoic Acid		Placebo
Arm/Group Description	28 subjects receive oral lipoic acid 1200mg daily lipoic acid: 1200 mg taken by mouth daily starting on day one of the study and ending on the last day of study participation.		28 subjects receive placebo daily Placebo: The placebo comparator will be taken by mouth daily starting on day one of the study and ending on the last day of study participation
All Cause Mortality
	Lipoic Acid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lipoic Acid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/28 (32.1%)		6/26 (23.1%)
Gastrointestinal disorders
Emesis	1/28 (3.6%)	1	0/26 (0%)	0
Appendicitis	1/28 (3.6%)	1	0/26 (0%)	0
Infections and infestations
Urinary Tract Infection	2/28 (7.1%)	2	1/26 (3.8%)	1
Pneumonia	0/28 (0%)	0	1/26 (3.8%)	1
Injury, poisoning and procedural complications
Fall	0/28 (0%)	0	2/26 (7.7%)	2
Burn	0/28 (0%)	0	1/26 (3.8%)	1
Investigations
CPK elevation	0/28 (0%)	0	1/26 (3.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer	1/28 (3.6%)	1	0/26 (0%)	0
Psychiatric disorders
Suicidal Ideation	1/28 (3.6%)	1	0/26 (0%)	0
Confusion	1/28 (3.6%)	1	0/26 (0%)	0
Renal and urinary disorders
Renal Failure	1/28 (3.6%)	1	0/26 (0%)	0
Proteinuria	1/28 (3.6%)	1	0/26 (0%)	0
Other (Not Including Serious) Adverse Events
	Lipoic Acid		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/28 (89.3%)		22/26 (84.6%)
Ear and labyrinth disorders
Vertigo	0/28 (0%)	0	1/26 (3.8%)	1
Endocrine disorders
Hypothyroidism	0/28 (0%)	0	1/26 (3.8%)	1
Eye disorders
Optic Neuritis	1/28 (3.6%)	1	0/26 (0%)	0
Peripapillary choroidal neovascularization	0/28 (0%)	0	1/26 (3.8%)	1
R. Eye Visual Sx	1/28 (3.6%)	1	0/26 (0%)	0
Gastrointestinal disorders
Constipation	1/28 (3.6%)	1	0/26 (0%)	0
Diarrhea	1/28 (3.6%)	1	2/26 (7.7%)	2
Dyspepsia	0/28 (0%)	0	1/26 (3.8%)	1
Gastritis	2/28 (7.1%)	3	0/26 (0%)	0
Gatroparesis	1/28 (3.6%)	1	0/26 (0%)	0
GERD	0/28 (0%)	0	1/26 (3.8%)	1
Indigestion	1/28 (3.6%)	1	0/26 (0%)	0
GI upset	2/28 (7.1%)	2	0/26 (0%)	0
Nausea	4/28 (14.3%)	4	0/26 (0%)	0
Vomiting	2/28 (7.1%)	3	0/26 (0%)	0
General disorders
Edema of lower limbs	1/28 (3.6%)	1	0/26 (0%)	0
Fatigue	0/28 (0%)	0	1/26 (3.8%)	1
Flu-like symptoms	3/28 (10.7%)	5	2/26 (7.7%)	2
Hepatobiliary disorders
Gall bladder inflammation	1/28 (3.6%)	1	0/26 (0%)	0
Infections and infestations
Appendicitis	1/28 (3.6%)	1	0/26 (0%)	0
Eye Infection (stye)	0/28 (0%)	0	1/26 (3.8%)	1
Fungal skin infection	1/28 (3.6%)	1	0/26 (0%)	0
Lung Infection	1/28 (3.6%)	1	1/26 (3.8%)	1
Oral ulcers	0/28 (0%)	0	1/26 (3.8%)	1
Otis externa	1/28 (3.6%)	1	0/26 (0%)	0
Otis media	1/28 (3.6%)	1	1/26 (3.8%)	1
Urinary Tract Infection	6/28 (21.4%)	8	8/26 (30.8%)	11
Prostatitis	0/28 (0%)	0	1/26 (3.8%)	1
Sinusitis	1/28 (3.6%)	1	1/26 (3.8%)	1
Skin Infection	1/28 (3.6%)	1	1/26 (3.8%)	1
Vaginitis	0/28 (0%)	0	1/26 (3.8%)	1
Varicella Zoster	1/28 (3.6%)	1	0/26 (0%)	0
Viral Syndrome	1/28 (3.6%)	1	0/26 (0%)	0
Injury, poisoning and procedural complications
Fall	9/28 (32.1%)	11	13/26 (50%)	23
Spider Bite	1/28 (3.6%)	1	0/26 (0%)	0
Ankle Sprain	1/28 (3.6%)	1	0/26 (0%)	0
Abrasion (due to fall)	1/28 (3.6%)	1	0/26 (0%)	0
Left hand crush injury	1/28 (3.6%)	1	0/26 (0%)	0
Left Knee Meniscus Tear	0/28 (0%)	0	1/26 (3.8%)	1
Investigations
Elevated Liver Enzymes	1/28 (3.6%)	1	1/26 (3.8%)	1
Low WBC	1/28 (3.6%)	1	1/26 (3.8%)	1
Alkaline Phosphatase	1/28 (3.6%)	1	0/26 (0%)	0
Elevated creatinine	1/28 (3.6%)	1	0/26 (0%)	0
Metabolism and nutrition disorders
Anorexia	0/28 (0%)	0	1/26 (3.8%)	2
Dehydration	0/28 (0%)	0	1/26 (3.8%)	1
Hyperglycemia	1/28 (3.6%)	1	0/26 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoporosis	1/28 (3.6%)	1	0/26 (0%)	0
Tendonitis (Right Knee)	1/28 (3.6%)	1	0/26 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm: Prostate	1/28 (3.6%)	1	0/26 (0%)	0
Nervous system disorders
Dysegusia	1/28 (3.6%)	1	0/26 (0%)	0
Face tingling/numbness	0/28 (0%)	0	1/26 (3.8%)	1
MS Relapse	0/28 (0%)	0	1/26 (3.8%)	1
Radiculitis	1/28 (3.6%)	1	0/26 (0%)	0
Vasovagal reaction	0/28 (0%)	0	1/26 (3.8%)	1
Renal and urinary disorders
Kidney Stone with hydronephrosis	1/28 (3.6%)	1	0/26 (0%)	0
nocturnal enuresis	1/28 (3.6%)	1	0/26 (0%)	0
Proteinuria	1/28 (3.6%)	1	0/26 (0%)	0
Skin and subcutaneous tissue disorders
rash (maculo-papular)	2/28 (7.1%)	2	0/26 (0%)	0
Surgical and medical procedures
Hernia repair	1/28 (3.6%)	1	0/26 (0%)	0
surgical procedure- baclofen pump	1/28 (3.6%)	1	0/26 (0%)	0
Trigeminal neuralgia surgery	1/28 (3.6%)	1	0/26 (0%)	0
Benign nevi removed	1/28 (3.6%)	1	0/26 (0%)	0
Vascular disorders
Deep Vein Thrombosis	0/28 (0%)	0	1/26 (3.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.