Effect of Boswellia Serrata on Pain Intensity, Central and Peripheral Sensitization, and Pain Modulation in Healthy Volunteers - a Randomized, Double-blind, Placebo-controlled, Cross-over Pilot Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 12
- Locations
- 2
- Primary Endpoint
- Change in spontaneous pain intensity
Study Overview
Brief Summary
This planned study is based on a randomized, placebo-controlled cross-over design.
Boswellic acids, the triterpenes found in the gum resins of Boswellia serrata (family: Burseraceae), are traditionally used in the Indian Ayurvedic medicine system as antioxidants and anti-inflammatory agents for treating conditions such as rheumatoid arthritis, chronic bronchitis, asthma, and chronic inflammatory bowel diseases (ulcerative colitis and Crohn's disease). The β-configured pentacyclic triterpenic acids in B. serrata include 3-acetyl-11-keto-β-boswellic acid (AKBBA), 11-keto-β-boswellic acid (KBBA), β-boswellic acid (BBA), and 3-acetyl-β-boswellic acid (ABBA). These compounds, which constitute approximately 14% of the lipophilic fractions of the B. serrata extract, are the major active components. Boswellia serrata is marketed as a food supplement in accordance with EU Directive 2002/46/EC. Several clinical studies have examined the efficacy of B. serrata in chronic pain conditions.
The data suggest a clinical analgesic efficacy, without, however, allowing conclusions about the underlying mechanisms. These have not yet been investigated in a human experimental pain model. The aim of the study is to investigate the influence of Boswellia serrata in peripheral and central sensitization, as well as descending inhibitory pathways by Quantitative Sensory Testing (QST). These findings are of great relevance for a better understanding of clinical efficacy.
The 'Capsaicin Pain Model' is a validated method for inducing short-term peripheral and central sensitization. As a non-invasive human pain model, it is therefore well suited for investigating the analgesic and anti-hyperalgesic effects of drugs.
Furthermore, the influence of Boswellia serrata on mood (depression, anxiety), sleep quality and psychological well-being will be investigated by using the psychological questionnaires Becks-Depression-Inventory, Becks-Anxiety-Inventory, Pittsburgh Sleep Quality Index and World Health Organization Well-Being Index (BDI-II, BAI, PSQI and WHO5) as secondary target variables.
Detailed Description
"Boswellic acids, the triterpenes found in the gum resins of Boswellia serrata (family: Burseraceae), are traditionally used in the Indian Ayurvedic medicine system as antioxidants and anti-inflammatory agents for treating conditions such as rheumatoid arthritis, chronic bronchitis, asthma, and chronic inflammatory bowel diseases (ulcerative colitis and Crohn's disease).
The β-configured pentacyclic triterpenic acids in B. serrata include 3-acetyl-11-keto-β-boswellic acid (AKBBA), 11-keto-β-boswellic acid (KBBA), β-boswellic acid (BBA), and 3-acetyl-β-boswellic acid (ABBA). These compounds, which make up about 14% of the lipophilic fractions of B. serrata extract, are the major active components. Various pharmacological studies suggest that the β-configured derivatives of boswellic acids from BSE exhibit significantly better efficacy than their corresponding α-isomers. Additionally, the anti-inflammatory effects of BSE are well-documented in animal models, particularly in the inhibition of carrageenan-induced paw edema.
The data suggest a clinical analgesic efficacy, without, however, allowing conclusions about the underlying mechanisms. These have not yet been investigated in a human experimental pain model. The aim of the study is to investigate the influence of B. serratain peripheral and central sensitization, as well as descending inhibitory pathways by Quantitative Sensory Testing (QST). These findings are of great relevance for a better understanding of clinical efficacy.
An effect on peripheral sensitization speaks in favor of use in acute somatic pain. However, if the effect can be explained by central mechanisms, its use would be recommended in chronic or neuropathic pain. For this purpose, "Capsaicin Pain model" is a validated method for achieving short-term peripheral and central sensitization. As a non-invasive human pain model, it is therefore well suited for investigating the analgesic and anti-hyperalgesic effects of drugs.
Furthermore, the influence of B. serrata on mood (depression, anxiety), sleep quality and psychological well-being will be investigated by using the psychological questionnaires Becks-Depression-Inventory, Becks-Anxiety-Inventory, Pittsburgh Sleep Quality Index and World Health Organization Well-Being Index (BDI-II, BAI, PSQI and WHO5) as secondary target variables.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age: ≥18 years
Exclusion Criteria
- •Not pregnant or breastfeeding
- •No renal or liver insufficiency
- •No neurological/dermatological/cardiovascular diseases
- •No chronic pain and/or use of analgesics
- •No use of anticoagulants
- •No use of antidepressants
- •No use of MAO inhibitors
- •No use of St. John's Wort
- •No use of medications affecting the CYP mechanism
- •No allergies to Boswellia serrata or capsaicin"
Outcomes
Primary Outcomes
Change in spontaneous pain intensity
Time Frame: Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model
is measured on a visual analogue scale (0 means no pain and 10 means the worst imaginable pain)
Secondary Outcomes
- Change of well-being score(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change in conditioned pain modulation(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change in Allodynia(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change in Hyperalgesia(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change in heat detection threshold(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change in heat pain threshold(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change of depression score(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change of anxiety score(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change of sleep quality score(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change in Allodynia(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change in Hyperalgesia(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change in heat detection threshold(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change in heat pain threshold(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change in conditioned pain modulation(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change of depression score(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change of anxiety score(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change of sleep quality score(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)
- Change of well-being score(Day 0 -->Day 28 before capsaicin pain model --> Day 28 1 hour after capsaicin pain model --> Day 56 -->Day 84 before capsaicin pain model -->Day 84 1 hour after capsaicin pain model)