HemophiliaNCT02569359
Efficacy and Safety of Shea Nut Oil in Hemophilic Arthropathy
A study testing shea nut oil extract in people with Hemophilia and Hemophilic Arthropathy, run by Tri-Service General Hospital (TSGH) at 1 site in Taiwan.
Trial summary
Recurrent hemarthrosis results in synovitis and destructive arthropathy in hemophilic patients. Prophylactic replacement, physical therapy, cyclooxygenase-2 (COX-2) inhibitors, corticosteroids, and radionucleotide synovectomy are some of the typical modalities used in the managements hemophilic synovitis and… Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Hemophilia, Hemophilic Arthropathy
- What is being tested?
- shea nut oil extract
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteTaiwan
- Study dates
- Apr 2016to Sep 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age 20 years and above
- hemophilia A or B patients who reported painful (VAS ≥ 3) hemophilic arthropathy in ankles, elbows or knees for at least 6 months.
Who cannot join
- presence of joint infections
- any surgery on the joint in preceding 6 months
- intra-articular HA injection within the past 6 months
- history of rheumatoid arthritis,
- gouty arthropathy
- presence of neoplasm,
Show all 12Show fewer
- allergy to shea nut oil production
- use of corticosteroids within 3 weeks prior to baseline and throughout the study
- use of anti-inflammatory agents 3 weeks prior to baseline and for the duration of the study,
- history of trauma associated with the signal joint,
- liver function tests greater than twice the upper limit of normal at baseline
- history of alcohol or substance abuse.
Trial locations and contacts
1 site in 1 country.
About this study
Recurrent hemarthrosis results in synovitis and destructive arthropathy in hemophilic patients. Prophylactic replacement, physical therapy, cyclooxygenase-2 (COX-2) inhibitors, corticosteroids, and radionucleotide synovectomy are some of the typical modalities used in the managements hemophilic synovitis and arthropathy. In clinical practice, the choice of non-steroidal anti-inflammatory drugs (NSAIDs) also needs to take into consideration the risk for cardiovascular events and should be used at the lowest effective dose and for the shortest duration.This study will investigate the safety and efficacy of Shea nut oil for the treatment of hemophilic arthropathy.
Read the detailed description
Hemophilia is an X-linked recessive bleeding disorder caused by a deficiency of coagulation factor VIII (hemophilia A) or IX (hemophilia B). Severe hemophilia patients may have frequent spontaneous bleeding episodes such as joint and muscle bleeding. Repeated joint bleeding leads to chronic synovitis, cartilage damage and bony destruction, which is associated with range of motion (ROM) limitation, pain, muscle atrophy, functional impairment and poor quality of life. Around 80% of all spontaneous joint bleeds occur in the ankles, knees and elbows. Hemophilic arthropathy is a multifactorial event and there is evidence to suggest that iron may play a major role with release of cytokines such as Interleukin-1, Interleukin-6, and tumor necrosis factor-α (TNF-α) eading to chronic proliferative synovitis, hypervascularity, and progressive arthropathy . Prophylactic replacement , physical therapy, COX-2 inhibitors , corticosteroids, and radionucleotide synovectomy are some of the typical modalities used in the managements hemophilic synovitis and arthropathy. The onset of joint bleedings in severe hemophilia occurs approximately 23 months of age and arthropathy could be marked in adolescents or young adults. Some hemophilia patients may either not be good candidates for surgery or may prefer not to have surgery. The traditional Africans have used African Shea tree and shea nuts oil extracts to treat arthritis. Shea nut oil contains are a mixture of fatty acid and cinnamic acid esters of such triterpene alcohols as α-amyrine, β-amyrine, butyrospermol, lupeol and to aminor extent, sterols, aliphatic alcohols, and karitene. Triterpene alcohols such as lupeol and α/β-amyrine have been shown to possess anti-inflammatory effects, especially in their esterified forms. In 1998, US Food and Drug Administration approved shea nut oil as a safe food additive. The shea nut oil used in this trial is a patented concentrate containing approximately 50% triterpenes derived from the seed of the shea tree, Vitellaria paradoxa. The most abundant triterpenes in shea nut oil areα-amyrin(54.6%), β-amyrin(12.3%), Lupeol(17%) plus their dihydro-derivatives. Cheras et al. reported that shea nut oil extract treatment over the 15 weeks of their random double-blind study in upper quartile of 89 osteoarthritis patients was effective in decreasing inflammation marker TNF-α (23.9% vs 6%, treatment vs placebo) and cartilage degradation marker C-terminal crosslinked telopeptide type II collagen (CTX-II) (28.7% vs an increase of 17.6%, treatment vs placebo). Chen and his colleagues carried out a 16-week study in 33 patients with osteoarthritis of knee joint and found shea nut oil was effective in increasing activity and thickness of vastus medialis, and decreasing pain and stiffness of knee joint. Late stage of hemophilic arthropathy is characterized by advanced cartilage degeneration and joint destruction. These effects on cartilage and subchondral bone are degenerative and inflammatory in nature, similar to the changes in osteoarthritis. Management of chronic hemophilic arthropathy is difficult. NSAIDs have been used with caution in patients with bleeding disorders because of their inhibition of platelet function and gastrointestinal side effects. In clinical practice, the choice of NSAIDs also needs to take into consideration the risk for cardiovascular events and should be used at the lowest effective dose and for the shortest duration. This study will investigate the safety and efficacy of Shea nut oil for the treatment of hemophilic arthropathy.
- Conditions
- Hemophilia, Hemophilic Arthropathy
- Being tested
- shea nut oil extract, Placebo
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
shea nut oil extractDietary supplement
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Shea nut oil | Experimental | 100% shea nut oil extract with 75% triterpene esters. Daily dosage is three 750 mg soft gel capsules (2250 mg/per day) taken in the morning for 3 months Receives: Dietary Supplement: shea nut oil extract |
| Placebo | Placebo comparator | placebo which comprised 100% canola oil or starch mixed soybean oil Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain (visual analogue scale) and Change from Baseline Pain at 1 &3 months
The pain intensity will be evaluated subjectively on a visual analogue scale (0-100mm).
Measured: baseline, 1 month, 3 months
Secondary outcomes (6)
CTX-II (ng/mmol creatinine) and Change from Baseline at 1 & 3 months
C-telopeptide fragments of type II collagen (CTX-II) in urine is a measure of type II collagen degradation and a biological marker of arthropathy.
Measured: baseline, 1 month, 3 months
Tumor Necrosis Factor alpha (pg/mL) and Change from Baseline at 1 & 3 months
TNF-alpha are one of inflammatory mediators that increase following hemarthrosis in hemophilic mice. Plasma samples will tested by ELISA.
Measured: baseline, 1 month, 3 months
Ultrasonographic synovial thickness (mm) and Change from Baseline at 1 &3 months
Synovial thickness (mm) by ultrasonography were evaluated from the lateral, middle, and medial aspects of the anterior suprapatellar recess
Measured: baseline, 1 month, 3 months
Synovial hyperemia (score) and Change from Baseline at 1& 3 months
Power Doppler assessment of selected synovial sites is carried out with settings standardized to a pulse repetition frequency of 700 Hz. The intensity of the blood flow in the synovium is scored into 0 to 3 (0=No flag; 1 = 1 flag; 2 = 2-3 flags; 3=>3 flags) adapted from Klukowska and Melchiorre et al
Measured: baseline, 1 month, 3 months
Short Form -36 score and Change from Baseline at 1 & 3 months
The SF-36 is filled out taking into account the person's condition in the last one month and scores range from 0 to 100, with higher scores indicating better health-related quality of life.
Measured: baseline, 1 month, 3 months
Hemophilia Joint Health Score (HJHS) and Change from Baseline at 1 & 3 months
The HJHS is a structured physical examination score evaluating the joint health in hemophilia patient. The score for each joint is the sum of the individual items including swelling, swelling duration, muscle atrophy, axial alignment, crepitus of motion, flexion loss \& extension loss, joint pain and strength. A score of 20 suggests the worst possible damage/impairment in the evaluating joint.
Measured: baseline, 1 month, 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2015 (estimated)
- Study startApr 2016
- Primary completionSep 2018
- Study completionSep 2018
Why it stopped: participants were not recruited enough
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HemophiliaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tri-Service General Hospital (TSGH)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tsung-Ying Li, Tri-Service General Hospital (TSGH)
- Investigators
- Tsung-Ying Li, Principal investigator, Hemophilia care and research center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02569359
- Sponsor's protocol ID
- 1-104-05-041
- Status last verified
- Apr 2021
- First submitted
- 1 Oct 2015
- Last updated
- 6 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Shea Nut Oil in Hemophilic Arthropathy
- ClinicalTrials.gov ID
- NCT02569359
- Acronym / sponsor ID
- 1-104-05-041
- Conditions
- Hemophilia, Hemophilic Arthropathy
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: participants were not recruited enough
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Tri-Service General Hospital (TSGH)University, hospital or other
- Study start
- Apr 2016 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 6 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recurrent hemarthrosis results in synovitis and destructive arthropathy in hemophilic patients. Prophylactic replacement, physical therapy, cyclooxygenase-2 (COX-2) inhibitors, corticosteroids, and radionucleotide synovectomy are some of the typical modalities used in the managements hemophilic synovitis and arthropathy. In clinical practice, the choice of non-steroidal anti-inflammatory drugs (NSAIDs) also needs to take into consideration the risk for cardiovascular events and should be used at the lowest effective dose and for the shortest duration.This study will investigate the safety and efficacy of Shea nut oil for the treatment of hemophilic arthropathy.
Detailed description
Hemophilia is an X-linked recessive bleeding disorder caused by a deficiency of coagulation factor VIII (hemophilia A) or IX (hemophilia B). Severe hemophilia patients may have frequent spontaneous bleeding episodes such as joint and muscle bleeding. Repeated joint bleeding leads to chronic synovitis, cartilage damage and bony destruction, which is associated with range of motion (ROM) limitation, pain, muscle atrophy, functional impairment and poor quality of life. Around 80% of all spontaneous joint bleeds occur in the ankles, knees and elbows. Hemophilic arthropathy is a multifactorial event and there is evidence to suggest that iron may play a major role with release of cytokines such as Interleukin-1, Interleukin-6, and tumor necrosis factor-α (TNF-α) eading to chronic proliferative synovitis, hypervascularity, and progressive arthropathy . Prophylactic replacement , physical therapy, COX-2 inhibitors , corticosteroids, and radionucleotide synovectomy are some of the typical modalities used in the managements hemophilic synovitis and arthropathy. The onset of joint bleedings in severe hemophilia occurs approximately 23 months of age and arthropathy could be marked in adolescents or young adults. Some hemophilia patients may either not be good candidates for surgery or may prefer not to have surgery. The traditional Africans have used African Shea tree and shea nuts oil extracts to treat arthritis. Shea nut oil contains are a mixture of fatty acid and cinnamic acid esters of such triterpene alcohols as α-amyrine, β-amyrine, butyrospermol, lupeol and to aminor extent, sterols, aliphatic alcohols, and karitene. Triterpene alcohols such as lupeol and α/β-amyrine have been shown to possess anti-inflammatory effects, especially in their esterified forms. In 1998, US Food and Drug Administration approved shea nut oil as a safe food additive. The shea nut oil used in this trial is a patented concentrate containing approximately 50% triterpenes derived from the seed of the shea tree, Vitellaria paradoxa. The most abundant triterpenes in shea nut oil areα-amyrin(54.6%), β-amyrin(12.3%), Lupeol(17%) plus their dihydro-derivatives. Cheras et al. reported that shea nut oil extract treatment over the 15 weeks of their random double-blind study in upper quartile of 89 osteoarthritis patients was effective in decreasing inflammation marker TNF-α (23.9% vs 6%, treatment vs placebo) and cartilage degradation marker C-terminal crosslinked telopeptide type II collagen (CTX-II) (28.7% vs an increase of 17.6%, treatment vs placebo). Chen and his colleagues carried out a 16-week study in 33 patients with osteoarthritis of knee joint and found shea nut oil was effective in increasing activity and thickness of vastus medialis, and decreasing pain and stiffness of knee joint. Late stage of hemophilic arthropathy is characterized by advanced cartilage degeneration and joint destruction. These effects on cartilage and subchondral bone are degenerative and inflammatory in nature, similar to the changes in osteoarthritis. Management of chronic hemophilic arthropathy is difficult. NSAIDs have been used with caution in patients with bleeding disorders because of their inhibition of platelet function and gastrointestinal side effects. In clinical practice, the choice of NSAIDs also needs to take into consideration the risk for cardiovascular events and should be used at the lowest effective dose and for the shortest duration. This study will investigate the safety and efficacy of Shea nut oil for the treatment of hemophilic arthropathy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Shea nut oil | Experimental | Dietary Supplement: shea nut oil extract100% shea nut oil extract with 75% triterpene esters. Daily dosage is three 750 mg soft gel capsules (2250 mg/per day) taken in the morning for 3 months |
| Placebo | Placebo comparator | Other: Placeboplacebo which comprised 100% canola oil or starch mixed soybean oil |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- age 20 years and above
- hemophilia A or B patients who reported painful (VAS ≥ 3) hemophilic arthropathy in ankles, elbows or knees for at least 6 months.
Key exclusion criteria (12 listed)
- presence of joint infections
- any surgery on the joint in preceding 6 months
- intra-articular HA injection within the past 6 months
- history of rheumatoid arthritis,
- gouty arthropathy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| shea nut oil extract | Dietary supplement | Shea nut oil |
| Placebo | Other | Placebo |
Primary outcome
Pain (visual analogue scale) and Change from Baseline Pain at 1 &3 months
Time frame: baseline, 1 month, 3 months
The pain intensity will be evaluated subjectively on a visual analogue scale (0-100mm).
6 secondary outcomes
CTX-II (ng/mmol creatinine) and Change from Baseline at 1 & 3 months
Time frame: baseline, 1 month, 3 months
Tumor Necrosis Factor alpha (pg/mL) and Change from Baseline at 1 & 3 months
Time frame: baseline, 1 month, 3 months
Ultrasonographic synovial thickness (mm) and Change from Baseline at 1 &3 months
Time frame: baseline, 1 month, 3 months
Synovial hyperemia (score) and Change from Baseline at 1& 3 months
Time frame: baseline, 1 month, 3 months
Short Form -36 score and Change from Baseline at 1 & 3 months
Time frame: baseline, 1 month, 3 months
Hemophilia Joint Health Score (HJHS) and Change from Baseline at 1 & 3 months
Time frame: baseline, 1 month, 3 months
Results and safety
The study was stopped early (reason given: participants were not recruited enough). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tsung-Ying Li principal investigator
Hemophilia care and research center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing shea nut oil extract in people with Hemophilia and Hemophilic Arthropathy, run by Tri-Service General Hospital (TSGH) at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: participants were not recruited enough). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain (visual analogue scale) and Change from Baseline Pain at 1 &3 months (time frame: baseline, 1 month, 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2021.