Antioxidant Therapy to Reduce Inflammation in Sickle Cell Disease

• Sponsor: UCSF Benioff Children's Hospital Oakland (Other)
• Overall Status: Completed
• CT.gov ID: NCT01054768
• Collaborator: National Center for Complementary and Integrative Health (NCCIH) (NIH)
• Enrollment: 37
• Location: 1
• Arms: 2
• Duration (Months): 44
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether alpha-lipoic acid and acetyl-L-carnitine will lower systemic inflammation in patients with Sickle Cell Disease by reducing oxidative stress, which will result in a decrease in the frequency of vaso-occlusive pain episodes and improve their quality of life.

Condition or Disease	Intervention/Treatment	Phase
Anemia, Sickle Cell	Drug: alpha-lipoic acid and acetyl-L-carnitine; Drug: Control	Phase 2

Detailed Description

People with sickle cell disease have more inflammation (a response of body tissues to injury or irritation) than people without sickle cell disease. This inflammation can be measured in the blood by checking the level of a protein called C reactive protein as well as other changes we see in blood due to inflammation (such as changes in platelets and other cells). There is even more inflammation during sickle-related complications (like pain or acute chest syndrome). We want to test if inflammation in people with sickle cell disease can be reduced by the use of antioxidant compounds.

Antioxidants are nutrients (certain vitamins, minerals and enzymes) that can counteract the effects of oxidative stress arising from free radicals in our cells. The formation of free radicals is a normal cell process, but uncontrolled oxidative stress can cause problems for us. One such harmful problem is inflammation.

We know from other research studies that antioxidants help with some conditions related to inflammation. In this study the antioxidant being tested is a combination of alpha-lipoic acid and acetyl-L-carnitine, both of which are natural parts of many of the foods we eat and are needed by our cells to make energy from food.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Antioxidant Therapy to Reduce Inflammation in Sickle Cell Disease
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: alpha-lipoic acid and acetyl-L-carnitine alpha-lipoic acid and acetyl-L-carnitine1400 mg tablet twice a day for 6 months.	Drug: alpha-lipoic acid and acetyl-L-carnitine; none to report; Other Names: Experimental
Placebo Comparator: Placebo 1400 mg placebo tablet twice a day for 6 months.	Drug: Control; none to report; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. C-Reactive Protein [6 months]

   C-Reactive Protein (CRP) was measured by a clinical laboratory. Measuring the quantity of serum CRP is helpful in recognizing inflammatory states.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Proven diagnosis of sickle cell disease, either homozygous sickle disease or Hb S Beta zero thalassemia genotype

• Age at entry at least 14 years. Younger children will not be included since the combination alpha-lipoic acid and acetyl-L-carnitine tablets are not available in a smaller dose at this time.

Exclusion Criteria:

• More than 3 packed red blood transfusions in the past 12 months

• Coexisting illness that could contribute to inflammation. These include chronic hepatitis, lupus, arthritis, inflammatory bowel disease, chronic osteomyelitis, and other similar conditions.

• Acute sickle cell disease related symptoms requiring a hospital visit in the past 4 weeks

• Women who are pregnant, attempting to get pregnant, or breast feeding

• Active participation in other investigational drug or device studies

• Participants who start hydroxyurea or regular transfusion therapy during the course of the study on the recommendation of their primary hematologist will be ineligible for further participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital & Research Center Oakland	Oakland	California	United States	94609

Sponsors and Collaborators

• UCSF Benioff Children's Hospital Oakland
• National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: Elliott Vichinsky, M.D., UCSF Benioff Children's Hospital Oakland
• Study Chair: Bruce N. Ames, Ph.D., UCSF Benioff Children's Hospital Oakland
• Study Director: Ashutosh Lal, M.D., UCSF Benioff Children's Hospital Oakland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: UCSF Benioff Children's Hospital Oakland
• ClinicalTrials.gov Identifier: NCT01054768
• Other Study ID Numbers: 2009-003; 1R21AT004493-01
• First Posted: Jan 22, 2010
• Last Update Posted: Aug 3, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by UCSF Benioff Children's Hospital Oakland: Antioxidant; Inflammation; Sickle Cell Disease; Oxidative Stress; Cytokines; anti-inflammatory; Acetylcarnitine
• Additional relevant MeSH terms: Anemia, Sickle Cell; Inflammation; Thioctic Acid; Acetylcarnitine

Study Results

Participant Flow

Recruitment Details	First subject was enrolled 08/10/09. Length of subject involvement was 7 months. Each subject was seen once a month at Children's Hospital & Research Center Oakland
Pre-assignment Detail	Exclusions included those with 3 packed red blood transfusions in the past year, illness that could contribute to inflammation, acute sickle cell disease related symptoms requiring a hospital visit, those pregnant or breast feeding, or in other investigational drug or device studies, participants on hydroxyurea or a regular transfusion therapy.

Arm/Group Title	Alpha-lipoic Acid and Acetyl-L-carnitine	Placebo
Arm/Group Description	alpha-lipoic acid and acetyl-L-carnitine 1400 mg tablet twice a day for 6 months. alpha-lipoic acid and acetyl-L-carnitine: none to report	1400 mg placebo tablet twice a day for 6 months. Placebo: none to report
Period Title: Overall Study
STARTED	17	20
COMPLETED	9	17
NOT COMPLETED	8	3

Baseline Characteristics

Arm/Group Title	Alpha-lipoic Acid and Acetyl-L-carnitine	Placebo	Total
Arm/Group Description	alpha-lipoic acid and acetyl-L-carnitine 1400 mg tablet twice a day for 6 months. alpha-lipoic acid and acetyl-L-carnitine: none to report	1400 mg placebo tablet twice a day for 6 months. Placebo: none to report	Total of all reporting groups
Overall Participants	17	20	37
Age (Count of Participants)
<=18 years	1 5.9%	4 20%	5 13.5%
Between 18 and 65 years	16 94.1%	16 80%	32 86.5%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	7 41.2%	8 40%	15 40.5%
Male	10 58.8%	12 60%	22 59.5%

Outcome Measures

1. Primary Outcome

Title	C-Reactive Protein
Description	C-Reactive Protein (CRP) was measured by a clinical laboratory. Measuring the quantity of serum CRP is helpful in recognizing inflammatory states.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Reason for discontinuation: started transfusions (2), alternative treatment (2), adverse events (4), subject preference (3).

Arm/Group Title	Alpha-lipoic Acid and Acetyl-L-carnitine	Placebo
Arm/Group Description	alpha-lipoic acid and acetyl-L-carnitine 1400 mg tablet twice a day for 6 months. alpha-lipoic acid and acetyl-L-carnitine: none to report	1400 mg placebo tablet twice a day for 6 months. Placebo: none to report
Measure Participants	9	17
Mean (Standard Deviation) [mg/l]	11.4 (20.9)	6.8 (10.3)

Adverse Events

Time Frame	2 years
Arm/Group Title	Alpha-lipoic Acid and Acetyl-L-carnitine		Placebo
Arm/Group Description	alpha-lipoic acid and acetyl-L-carnitine 1400 mg tablet twice a day for 6 months. alpha-lipoic acid and acetyl-L-carnitine: none to report		1400 mg placebo tablet twice a day for 6 months. Placebo: none to report
All Cause Mortality
	Alpha-lipoic Acid and Acetyl-L-carnitine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/20 (0%)
Serious Adverse Events
	Alpha-lipoic Acid and Acetyl-L-carnitine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/17 (47.1%)		9/20 (45%)
Blood and lymphatic system disorders
Vaso-occlusive pain	6/17 (35.3%)	13	9/20 (45%)	13
Respiratory, thoracic and mediastinal disorders
Pneumonia/Acute Chest Syndrome	2/17 (11.8%)	2	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	Alpha-lipoic Acid and Acetyl-L-carnitine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/17 (35.3%)		12/20 (60%)
Gastrointestinal disorders
Nausea	2/17 (11.8%)	2	7/20 (35%)	7
Renal and urinary disorders
Urinary Urgency/UTI	2/17 (11.8%)	2	5/20 (25%)	6
Respiratory, thoracic and mediastinal disorders
Respiratory Symptoms	3/17 (17.6%)	3	9/20 (45%)	12

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.