Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT03924596 |
| Other study ID # |
IG/DVC/MRC/19/03 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
September 2019 |
| Est. completion date |
February 2021 |
Study information
| Verified date |
April 2019 |
| Source |
Sultan Qaboos University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Frankincense, or olibanum, is the oleogum resin that is harvested from several different
trees, an aromatic resin obtained from trees of the genus Boswellia. The word frankincense is
derived from the ancient French name "frankincense," meaning "pure incense." Frankincense is
also known in Arabic as "luban,". Luban has been reported to have anti-inflammatory,
sedative, antibacterial, and anti-cancer activities. The aim of the present study is to treat
renal stones with Luban (Boswellia) given as capsules of active oils.
This is a clinical Phase I & II (Safety, Efficacy) double-blind simple-randomized controlled
treatment trial, where 100 participants with renal stones (50 Radiopaque and 50 Radiolucent
stones) will be included in the study and divided between two treatment groups: Standard
treatment (Uralyt-U) and new treatment (Luban). Participants with stone size less than 10 mm
will be include; and participants with renal pathology or comorbidities (DM, CKD, multiple
renal cysts, renal tumors) will be excluded. The outcome measures of the study will be: the
primary end point (effect) is reduction of stone size by 50% or complete disappearance after
1 years of treatment; and the secondary end point (toxicity) is the participants intolerance
of the treatment or development of side effects. If this study proves an effect of Luban on
renal stones it will be an evolution in the management of renal stones by a natural, simple,
harmless easily available method.
Description:
Investigator Brochure of Olibanum (Boswellic Acid):
A. Clinical Research
Olibanum has been utilized as an important fixative in perfumes, soaps, creams, lotions, and
detergents in the leading products of the perfume and cosmetic industry, as it has an
oriental note in its scent. The interest of pharmaceutical companies created a third market
for olibanum. Since ancient times, it has been used in folk medicine for its antiseptic,
antiarthritic, and anti- inflammatory effects. For this reason, olibanum has gained
increasing attention from scientists in the last 20 years to better define its medical
effects and identify the constituents that are responsible for these effects.4 Animal studies
and pilot clinical trials support the potential of B. serrata gum resin extract (BSE) for the
treatment of a variety of inflammatory diseases like inflammatory bowel disease, rheumatoid
arthritis, osteoarthritis and asthma.5 Moreover, in 2002 the European Medicines Agency
classified BSE as an 'orphan drug' for the treatment of peritumoral brain oedema.6 The
pharmacological effects of BSE have been mainly attributed to boswellic acids, especially
11-keto-b-boswellic acid (KBA) and acetyl-11-keto-b-boswellic acid (AKBA), which were
proposed as selective 5-lipoxygenase (5-LO) inhibitors.7 Thus, instead of 5-LO inhibition by
AKBA, inhibition of cathepsin G (catG) and acid might represent the principal mode of action
of BSE.8 The gum resin is obtained by incision of the stem or branches of B. serrata.
Following air-drying, the gum resin exudate consists of translucent, roundish or irregularly
shaped, variable size pieces of up to 3 cm. The main components are volatile oils (5-15%),
pure resin (55-66%) and mucus (12-23%). The gum resin typically contains 30% boswellic
acids.9 The β-boswellic acid, is considered to be one of the main active components of
frankincense. These are some of the chemical compounds present in frankincense: acid resin
(56 per cent), soluble in alcohol and having the formula C20H32O4; gum (similar to gum
Arabic) 30-36%; 3-acetyl-beta-boswellic acid (Boswellia sacra); alpha-boswellic acid
(Boswellia sacra); 4-O-methyl-glucuronic acid (Boswellia sacra); incensole acetate
phellandrene .The work of Ibn Sina (Avicenna) of the 11th century refers to the use of
frankincense in inflammation and infection of the urinary tract.10 In Kenya it is used for
dressing wounds and, when mixed with sesame oil, is taken to reduce the loss of blood in the
urine from schistosomiasis infestation. The Antimicrobial activity of Boswellia resin have
been suggested by studies.11 The biological activities of essential oils including:
Antioxidant activity; Acetylcholinesterase inhibition; Antimicrobial activity and Antifungal
activity.11 The antibacterial activity of oleo-gum resins of B. sacra, known as Hoojri,
Najdi, Shathari, and Shaabi has been reported.3 All the four oils were effective against both
Gram-positive and Gram-negative bacteria. The clinical isolates of Bacillus subtilis,
Micrococcus luteus, Staphylococcus aureus, Klebsiella pneumoniae, and Enterobacter aerogenes
were sensitive to all the oils, while those of Pseudomonas aeruginosa, Escherichia coli, and
Proteus vulgaris were resistant to the Shathari, Najdi, and Hoojri oils, respectively.3
Anticancer activity: multiple pathways that could be activated by frankincense oil to induce
bladder cancer cell death.12 The anti-inflammatory and analgesic activities of Boswellia
serrata, and B. sacra have been reported.13 Recently It has been shown that the aqueous stem
bark extract of Boswellia papyrifera oral administration has a Nephro-curative effects on
acetaminophen-induced kidney damage in rats and that effect was found to be dose- and time-
dependent.14 In addition, Oleo-gum-resin of Boswellia serrata Roxb induced Reno-protective
action against Gentamicin induced nephrotoxicity in Albino rats.15 Also Zingiber officinale
Roscoe (Ginger), Arabic gum (AG), and Boswellia have been found to be beneficial adjuvant
therapy in participants with acute renal failure and CRF to prevent disease progression and
delay the need for renal replacement therapy.16
B. Basic Research
Morphological studies of frankincense on kidney stones done at a preclinical setup, results
attached in Appendix I.
Research Methodology Problem: Renal stones are common and people prefer non-surgical
treatment approaches
Aim of study (Question): Can we treat renal stones with a harmless easily available natural
product like Luban (Boswellia) given as capsules of active oils? And can Luban protect the
kidneys from the sequel of inflammation and kidney damage induced by nephrolithiasis.
Study design
A. Study Groups (Arms) and interventions:
This is a clinical Phase I & II (Safety, Efficacy) double-blind simple-randomized controlled
treatment trial involving 100 participants in 4 groups (25 participants each group)
Group 1: 25 participants with radiopaque stones (Calcium Oxalate) treated with Luban
Group 2: 25 participants with radiopaque stones (Calcium Oxalate) treated with Uralyt-U
Group 3: 25 participants with radiolucent stones (Uric acid) treated with Luban
Group 4: 25 participants with radiolucent stones (Uric acid) treated with Uralyt-U
B. Inclusion criteria:
• Participants with renal stones equal or less than 10mm in size
C. Exclusion criteria:
- Participants with renal pathology (Renal anomalies, multiple renal cysts, renal tumors)
- Participants with comorbidities (DM, CKD)
D. Withdrawal criteria
- Participants under treatment protocol who pass a stone and documented to be the stone
under evaluation
- Participants who have uncontrolled pain with the need for surgical intervention to
remove the stone
E. Outcome measures
- Primary Endpoints: The primary end point (effect) is reduction of stone size by 50% or
complete disappearance after 1 years of treatment.
- Secondary Endpoints: The secondary end point (toxicity) is the participants intolerance
of the treatment or development of side effects.
F. Measurements:
Participants factor: Age (18-70 years), Sex, comorbidities, first time or recurrent former of
stone, presentation
Stone factor: size in mm, location, composition (stone analysis if possible), Side of kidney.
G. Data handling and record keeping:
Source data (participants data collected) will be recorded in the case report form, CRF (data
collection sheet) specified for each participant. The CRF will be kept in a key-protected
file cabinet and a scanned electronic copy in a password-protected computer until analysis is
carried out. Source data verification will be carried out from the source data if any
inconsistencies arise by the means of regular research team meeting and review of the
collected data. Correct and consistent completion of participant initials and study ID number
will be regularly checked by the designated research nurse.
H. Safety assessment:
The principal investigator along with the sponsor will ensure the right and safety of the
participants are protected and the study data are accurate and complete and the study is
being conducted in compliance with the protocol and Good Clinical Practice (GCP), and
regulatory requirements. The study will have a very strict adverse reaction reporting system
to identify any risks or side effects that may occur and not recognized before. This will be
done by a continuous record of a table of anticipated and unanticipated serious adverse
events grouped by organ system, with number and frequency of such event in each arm of the
clinical trial. The principal investigator will be regularly updated to take decisions about
the actions to be taken in case of a serious risk to patients occurred. All adverse events
(AEs) and adverse reactions (AR), wither serious or not and wither suspected or unexpected,
that may have been caused by the study conduct or the investigational medicinal product will
be filled in the specified forms and reported to the sponsor immediately.
I. Procedures for reporting deviations from the original plan:
Deviations from the protocol and GCP will be monitored and corrected if become apparent.
Every effort will be done to ensure compliance with the protocol and preparation for the
unexpected will be anticipated by a systematic approach of dealing and documenting the
devotions in the participants study file.
J. Quality control and quality assurance:
Serious breaches that have the potential to affect the safety of participants or integrity of
the study will be monitor closely and if occur will be investigated, reported to the sponsor
and acted upon immediately. The principal investigator will be leading the role in the
resolution of a serious breach and actions will be recorded in the participants study file.
Statistical analysis:
For each type of stones (radiopaque, radiolucent), the two independent treatment arms (Luban
and conventional) will be compared for the two categorical outcomes of no effect or good
effect, with good effect defined as reduction of stone size by 50% or complete disappearance
after 1 year of treatment. The Chi-squared test will be used to calculate wither the two
treatment groups are the same or different and 95% confidence interval will be calculated.
The significance level will be at p < 0.05. The analysis will be based on intention-to-treat
basis (participants will be analyzed in their original group even if they deviate from the
protocol). An interim analysis of the results will be done at 6 months of follow up to look
for any serious adverse effects.
Methods and Randomization:
Participants who satisfy the study criteria will be recruited over a period of one year
(September 2019 to September 2020). They will be randomly distributed to either the Luban
treatment (AKBA-Incense 2 capsules daily, 30% 3-acetyl-11-keto-ß-boswellic acid, from
ZeinPharma) or the conventional treatment Uralyt-U (Potassium Sodium Hydrogen Citrate, 10g
orally in 3 divided doses with pH target 6.2-6.8 for Calcium Oxalate stones and 7.0-7.2 for
Uric Acid stones) as a positive control, using a computer-generated list of random numbers
with even number for Luban treatment. Before inclusion: blood (Creatinine, Urea, K, Na, Ca,
P) and urine (urine analysis, urine culture) tests, Radiological (x-ray KUB, US abdomen, CT
abdomen) will be carried out. Participants will be followed up every 3 months for 1 year.
Each visit the following will be done: clinical and physical assessment, blood tests, urine
tests and CT abdomen.
