L-Glutamine Therapy for Sickle Cell Anemia

Sponsor
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Other)
Overall Status
Terminated
CT.gov ID
NCT00586209
Collaborator
Emmaus Medical, Inc. (Industry)
15
1
2
68.8
0.2

Study Details

Study Description

Brief Summary

The primary purpose is to evaluate the effect of L-glutamine therapy on exercise endurance and breath by breath exercise response of sickle cell anemia patients

The secondary purpose is to assess the effect of L-glutamine on incidence of painful crises; level of chronic pain, and amount of daily requirement for narcotics.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a phase II, prospective, randomized, double-blind, placebo-controlled, parallel-group,study to evaluate the safety and efficacy of oral L-glutamine therapy for patients with sickle cell anemia or sickle β°-thalassemia who are at least 18 years old with focus on the aspect of exercise endurance. In this study, the patients will orally take L-glutamine or placebo twice daily, and clinical and hematological parameters will be monitored. The adverse events,especially those attributable to L-glutamine therapy, will also be monitored.

The data obtained will be essential in understanding the role of L-glutamine in therapy for sickle cell anemia and sickle β°-thalassemia.

Study Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase II, Prospective, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Study of L Glutamine Therapy for Sickle Cell Anemia and Sickle ß0-Thalassemia
Actual Study Start Date :
Feb 6, 2004
Actual Primary Completion Date :
Aug 27, 2008
Actual Study Completion Date :
Nov 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: L-glutamine

L-glutamine group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily

Drug: L-Glutamine
L-Glutamine at: 5 g 2X daily (17-33.3 Kg) 10 g 2x daily (33.4-66.6 Kg) 15 g 2x daily (>66.7 kg)

Placebo Comparator: Placebo

Maltodextrin group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily

Drug: Placebo
Placebo (75% Maltodextrin, 24.5 % Starch, 0.5% Tricalcium Phosphate) - given at the same dosage as L-glutamine

Outcome Measures

Primary Outcome Measures

  1. Effect of L-glutamine Therapy on Exercise Endurance of Sickle Cell Anemia Patients [Baseline, Weeks 8 and 12]

    Exercise endurance will be examined at each visit. Change from baseline will be reported at weeks 8 and 12

  2. Effect of L-glutamine Therapy on Breath by Breath Exercise of Sickle Cell Patients [Baseline, Weeks 18 and 12]

    Breath by breath exercise will be examined at each visit. Change from baseline will be reported at weeks 8 and 12

Secondary Outcome Measures

  1. Effect of Oral L-glutamine on Incidence of Painful Crises [From Week 0 through Week 12]

    Incidence of panful crises will be assessed at each visit.

  2. Effect of Oral L-glutamine on Amount of Daily Requirement for Narcotics [From Week 0 through Week 20]

    Amount of daily requirement for narcotics will assessed at each visit.

  3. Effect of Oral L-glutamine on Level of Chronic Pain [From Week 0 to Week 12]

    Level of chronic pain will be assessed at each visit.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

To be eligible to participate in the study, a patient must meet all of the following inclusion criteria:

  • Patient is at least 18 years of age.

  • Patient has been diagnosed with sickle cell anemia or sickle ß0-thalassemia (documented by hemoglobin electrophoresis).

  • Patient has had at least two episodes of painful crises within 12 months of the screening visit.

  • If the patient has been treated with an anti-sickling agent within three months of the screening visit, the therapy must have been continuous for at least three months with the intent to continue for the next 14 months.

  • Patient or the patient's legally authorized representative has given written informed consent.

  • If the patient is a female of child-bearing potential, she agrees to practice a recognized form of birth control during the course of the study.

  • Patient is able to perform exercise tolerance test

Exclusion Criteria:
If the patient meets any of the following criteria, the patient must not be enrolled:
  • Patient has a significant medical condition that required hospitalization (other than sickle painful crisis) within two months of the screening visit.

  • Patient has diabetes mellitus with untreated fasting blood sugar >115 mg/dL.

  • Patient has prothrombin time International Normalized Ratio (INR) > 2.0.

  • Patient has serum albumin < 3.0 g/dl.

  • Patient has received any blood products within three weeks of the screening visit.

  • Patient has a history of uncontrolled liver disease or renal insufficiency.

  • Patient is pregnant or lactating.

  • Patient has been treated with an experimental anti-sickling medication/treatment (except hydroxyurea) within 30 days of the screening visit.

  • Patient has been treated with an experimental drug within 30 days of the screening visit.

  • There are factors that would, in the judgment of the investigator, make it difficult for the patient to comply with the requirements of the study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 LA Biomed at Harbor-UCLA Medical Center Torrance California United States 90502

Sponsors and Collaborators

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
  • Emmaus Medical, Inc.

Investigators

  • Principal Investigator: Yutaka Niihara, MD, LaBiomed At Harbor-UCLA Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
yutaka niihara, President, Emmaus Medical, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
ClinicalTrials.gov Identifier:
NCT00586209
Other Study ID Numbers:
  • 10511-01RY
First Posted:
Jan 4, 2008
Last Update Posted:
Feb 2, 2021
Last Verified:
Feb 1, 2021
Keywords provided by yutaka niihara, President, Emmaus Medical, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title L-glutamine Placebo
Arm/Group Description L-glutamine group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily L-Glutamine: L-Glutamine at: 5 g 2X daily (17-33.3 Kg) 10 g 2x daily (33.4-66.6 Kg) 15 g 2x daily (>66.7 kg) Maltodextrin group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily Placebo: Placebo (75% Maltodextrin, 24.5 % Starch, 0.5% Tricalcium Phosphate) - given at the same dosage as L-glutamine
Period Title: Overall Study
STARTED 5 10
COMPLETED 5 10
NOT COMPLETED 0 0

Baseline Characteristics

Arm/Group Title L-glutamine Placebo Total
Arm/Group Description L-glutamine group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily L-Glutamine: L-Glutamine at: 5 g 2X daily (17-33.3 Kg) 10 g 2x daily (33.4-66.6 Kg) 15 g 2x daily (>66.7 kg) Maltodextrin group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily Placebo: Placebo (75% Maltodextrin, 24.5 % Starch, 0.5% Tricalcium Phosphate) - given at the same dosage as L-glutamine Total of all reporting groups
Overall Participants 5 10 15
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
5
100%
10
100%
15
100%
>=65 years
0
0%
0
0%
0
0%
Sex: Female, Male (Count of Participants)
Female
3
60%
5
50%
8
53.3%
Male
2
40%
5
50%
7
46.7%
Region of Enrollment (participants) [Number]
United States
5
100%
10
100%
15
100%

Outcome Measures

1. Primary Outcome
Title Effect of L-glutamine Therapy on Exercise Endurance of Sickle Cell Anemia Patients
Description Exercise endurance will be examined at each visit. Change from baseline will be reported at weeks 8 and 12
Time Frame Baseline, Weeks 8 and 12

Outcome Measure Data

Analysis Population Description
The study was terminated by the Sponsor's business decision prior to achieving the planned enrollment. Due to this the data was not collected and not analyzed. However safety data was collected and analyzed to gather data on the safety of L-glutamine in sickle cell patients.
Arm/Group Title L-glutamine Placebo
Arm/Group Description L-glutamine group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily L-Glutamine: L-Glutamine at: 5 g 2X daily (17-33.3 Kg) 10 g 2x daily (33.4-66.6 Kg) 15 g 2x daily (>66.7 kg) Maltodextrin group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily Placebo: Placebo (75% Maltodextrin, 24.5 % Starch, 0.5% Tricalcium Phosphate) - given at the same dosage as L-glutamine
Measure Participants 0 0
2. Primary Outcome
Title Effect of L-glutamine Therapy on Breath by Breath Exercise of Sickle Cell Patients
Description Breath by breath exercise will be examined at each visit. Change from baseline will be reported at weeks 8 and 12
Time Frame Baseline, Weeks 18 and 12

Outcome Measure Data

Analysis Population Description
The study was terminated by the Sponsor's business decision prior to achieving the planned enrollment. Due to this the data was not collected and not analyzed. However safety data was collected and analyzed to gather data on the safety of L-glutamine in sickle cell patients.
Arm/Group Title L-glutamine Placebo
Arm/Group Description L-glutamine group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily L-Glutamine: L-Glutamine at: 5 g 2X daily (17-33.3 Kg) 10 g 2x daily (33.4-66.6 Kg) 15 g 2x daily (>66.7 kg) Maltodextrin group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily Placebo: Placebo (75% Maltodextrin, 24.5 % Starch, 0.5% Tricalcium Phosphate) - given at the same dosage as L-glutamine
Measure Participants 0 0
3. Secondary Outcome
Title Effect of Oral L-glutamine on Incidence of Painful Crises
Description Incidence of panful crises will be assessed at each visit.
Time Frame From Week 0 through Week 12

Outcome Measure Data

Analysis Population Description
The study was terminated by the Sponsor's business decision prior to achieving the planned enrollment. Due to this the data was not collected and not analyzed. However safety data was collected and analyzed to gather data on the safety of L-glutamine in sickle cell patients.
Arm/Group Title L-glutamine Placebo
Arm/Group Description L-glutamine group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily L-Glutamine: L-Glutamine at: 5 g 2X daily (17-33.3 Kg) 10 g 2x daily (33.4-66.6 Kg) 15 g 2x daily (>66.7 kg) Maltodextrin group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily Placebo: Placebo (75% Maltodextrin, 24.5 % Starch, 0.5% Tricalcium Phosphate) - given at the same dosage as L-glutamine
Measure Participants 0 0
4. Secondary Outcome
Title Effect of Oral L-glutamine on Amount of Daily Requirement for Narcotics
Description Amount of daily requirement for narcotics will assessed at each visit.
Time Frame From Week 0 through Week 20

Outcome Measure Data

Analysis Population Description
The study was terminated by the Sponsor's business decision prior to achieving the planned enrollment. Due to this the data was not collected and not analyzed. However safety data was collected and analyzed to gather data on the safety of L-glutamine in sickle cell patients.
Arm/Group Title L-glutamine Placebo
Arm/Group Description L-glutamine group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily L-Glutamine: L-Glutamine at: 5 g 2X daily (17-33.3 Kg) 10 g 2x daily (33.4-66.6 Kg) 15 g 2x daily (>66.7 kg) Maltodextrin group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily Placebo: Placebo (75% Maltodextrin, 24.5 % Starch, 0.5% Tricalcium Phosphate) - given at the same dosage as L-glutamine
Measure Participants 0 0
5. Secondary Outcome
Title Effect of Oral L-glutamine on Level of Chronic Pain
Description Level of chronic pain will be assessed at each visit.
Time Frame From Week 0 to Week 12

Outcome Measure Data

Analysis Population Description
The study was terminated by the Sponsor's business decision prior to achieving the planned enrollment. Due to this the data was not collected and not analyzed. However safety data was collected and analyzed to gather data on the safety of L-glutamine in sickle cell patients.
Arm/Group Title L-glutamine Placebo
Arm/Group Description L-glutamine group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily L-Glutamine: L-Glutamine at: 5 g 2X daily (17-33.3 Kg) 10 g 2x daily (33.4-66.6 Kg) 15 g 2x daily (>66.7 kg) Maltodextrin group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily Placebo: Placebo (75% Maltodextrin, 24.5 % Starch, 0.5% Tricalcium Phosphate) - given at the same dosage as L-glutamine
Measure Participants 0 0

Adverse Events

Time Frame Adverse events data were collected throughout the course of the study (53 weeks or about 1 year).
Adverse Event Reporting Description The Safety population will include all patients who received at least one dose of study medication.
Arm/Group Title L-glutamine Placebo
Arm/Group Description L-glutamine group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily L-Glutamine: L-Glutamine at: 5 g 2X daily (17-33.3 Kg) 10 g 2x daily (33.4-66.6 Kg) 15 g 2x daily (>66.7 kg) Maltodextrin group will be given at the following dosage: 17-33.3 kg at 5 g 2x daily 33.4-66.6 kg at 10 g 2X daily >66.7 at 15 g 2X daily Placebo: Placebo (75% Maltodextrin, 24.5 % Starch, 0.5% Tricalcium Phosphate) - given at the same dosage as L-glutamine
All Cause Mortality
L-glutamine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/5 (0%) 0/10 (0%)
Serious Adverse Events
L-glutamine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 2/5 (40%) 5/10 (50%)
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis 1/5 (20%) 1 4/10 (40%) 4
Investigations
Haemoglobin decreased 0/5 (0%) 0 1/10 (10%) 1
Vascular disorders
Hypertension 1/5 (20%) 1 0/10 (0%) 0
Other (Not Including Serious) Adverse Events
L-glutamine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 4/5 (80%) 7/10 (70%)
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis 1/5 (20%) 1 4/10 (40%) 4
Gastrointestinal disorders
Constipation 0/5 (0%) 0 1/10 (10%) 1
Diarrhoea 1/5 (20%) 1 0/10 (0%) 0
Mouth Pain 0/5 (0%) 0 1/10 (10%) 1
Nausea 1/5 (20%) 1 0/10 (0%) 0
Vomiting 1/5 (20%) 1 0/10 (0%) 0
General disorders
Chest pain 0/5 (0%) 0 1/10 (10%) 1
Infections and infestations
Clostridium difficile colitis 0/5 (0%) 0 1/10 (10%) 1
Fungal infection 1/5 (20%) 1 0/10 (0%) 0
Nasopharyngitis 1/5 (20%) 1 1/10 (10%) 1
Investigations
Cardiac murmur 1/5 (20%) 1 0/10 (0%) 0
Haemoglobin decreased 0/5 (0%) 0 1/10 (10%) 1
Musculoskeletal and connective tissue disorders
Arthralgia 0/5 (0%) 0 1/10 (10%) 1
Back pain 0/5 (0%) 0 1/10 (10%) 1
Nervous system disorders
Headache 0/5 (0%) 0 1/10 (10%) 1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 1/5 (20%) 1 0/10 (0%) 0
Cough 1/5 (20%) 1 0/10 (0%) 0
Surgical and medical procedures
Endodontic procedure 0/5 (0%) 0 1/10 (10%) 1
Vascular disorders
Hypertension 1/5 (20%) 1 0/10 (0%) 0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

Name/Title Yutaka Niihara, MD, MPH
Organization Emmaus Medical, Inc.
Phone 310-214-0065
Email yniihara@emmausmedical.com
Responsible Party:
yutaka niihara, President, Emmaus Medical, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
ClinicalTrials.gov Identifier:
NCT00586209
Other Study ID Numbers:
  • 10511-01RY
First Posted:
Jan 4, 2008
Last Update Posted:
Feb 2, 2021
Last Verified:
Feb 1, 2021