The Effects of Vitamin B6 Supplementation on Pain Thresholds and Tolerance

Testing the Effects of High-dose Vitamin B6 Supplements on Pain Thresholds and Tolerance in Healthy Adults

This clinical trial aims to explore the effect of Vitamin B6 supplementation on pain thresholds and tolerance in healthy adults using thermal and electrical stimulation. Researchers will compare a placebo group to high-dose Vitamin-B6 to see if vitamin B6 increases pain thresholds and tolerance.

Study Overview

• Status: Recruiting
• Conditions: Pain
• Intervention / Treatment: Drug: Vitamin B6 100 MG; Other: Placebo

Detailed Description

The main questions it aims to answer are:

• How does vitamin B6 affect pain thresholds and tolerance following a single 100mg dose?
• How does vitamin B6 affect pain thresholds following daily supplementation for up to a month?
• Does vitamin B6 supplementation affect measures related to the experience of pain, such as state anxiety, sleep, diet, and mood at different time points

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: David T Field, PhD; Phone Number: +441183785004; Email: d.t.field@reading.ac.uk
• Study Contact Backup: Name: Alex JA Cameron, MSc; Email: a.cameron@pgr.reading.ac.uk

Study Locations

• United Kingdom
  • Berkshire
    • Reading, Berkshire, United Kingdom, RG6 6AL
      • Recruiting
      • University of Reading
      • Contact: David T Field, PhD; Phone Number: +441183785004; Email: d.t.field@reading.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Over the age of 18 years
• Fluent speaker of English language

Exclusion Criteria:

• Under 18 years
• Presence or history of chronic pain
• Presence of neuropathic/nerve pain
• Raynaud's syndrome
• Using any vitamin supplementations that contain Vitamin B6 at more than the RDA, or combinations of B vitamins.
• On any medication that is GABA agonistic
• Any use of analgesic/anti-inflammatory medication up to 48 hours prior to any of the testing sessions.
• Any heart conditions
• Newly acquired tattoos on the pain stimulation site

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will consume a Placebo tablet matching the appearance of the Vitamin B6 tablets in the Experimental arm orally once daily for one month.	Other: Placebo; Placebo tablet containing microcrystalline cellulose
Experimental: Vitamin-B6; Participants will consume one high-dose Vitamin B6 100 mg tablet orally once daily for one month. Vitamin B6 will be provided as Pyridoxal-5'-Phosphate (PLP).	Drug: Vitamin B6 100 MG; Vitamin B6 in for the form of pyridoxal phosphate (PLP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thermal sensory threshold	Sensory threshold will be measured using thermal stimulation (heat stimulation). The starting temperature of the applied probe will be adjusted to the individual's skin temperature and then slowly increased (0.5 deg C/s) until the participant feels a slight warm sensation. For safety, the temperature will never exceed 50 deg C. The procedure will be repeated three times. The average change in temperature (in degree Celsius) needed for participants to perceive a warm sensation will be used as outcome measure. Low values will therefore indicate a high sensitivity to warmth, whereas high values will indicate a low warmth sensitivity.	This will be done at baseline, 4-5 hours, 3-5 days, 11-13, and 28-35 days after the start of the intervention
Thermal pain threshold	Pain threshold will be measured using thermal stimulation (heat stimulation). The starting temperature of the applied probe will be adjusted to the individual's skin temperature and then slowly increased (1 deg C/s) until the participant feels a slight pain/burning sensation. For safety, the temperature will never exceed 50 deg C. The procedure will be repeated three times. The average change in temperature (in degree Celsius) needed for participants to perceive a slight pain/burning sensation will be used as outcome measure. Low values will therefore indicate high pain sensitivity, whereas high values will indicate low pain sensitivity.	This will be done at baseline, 4-5 hours, 3-5 days, 11-13, and 28-35 days after the start of the intervention
Electrical pain sensitivity	Pain sensitivity will be measured using electrical stimulation. Starting at an initial intensity of 0.3 mA, the intensity of each subsequently applied electrical stimulus will be increased in steps of 0.3 mA each, with a maximum intensity of 10 mA. The procedure will be continued until the participant perceives the applied shock as moderately painful (equivalent to a pain rating of 5 out of 10 or higher). The procedure will be repeated three times. The average intensity (in mA) needed for participants to perceive a moderate pain sensation will be used as outcome measure. Low values will therefore indicate a high sensitivity to electrical stimulation, whereas high values will indicate a low pain sensitivity in response to electrical stimulation.	This will be done at baseline, 4-5 hours, 3-5 days, 11-13, and 28-35 days after the start of the intervention
Thermal pain tolerance	Pain tolerance will be measured using thermal stimulation (heat stimulation). The starting temperature of the applied probe will be adjusted to the individual's skin temperature and then slowly increased (1 deg C/s) until the participant feels that they can't tolerate the heat anymore. For safety, the temperature will never exceed 50 deg C. The procedure will be repeated three times. The average change in temperature (in degree Celsius) needed for participants to reach their pain tolerance will be used as outcome measure. Low values will therefore indicate low pain tolerance, whereas high values will indicate high pain tolerance.	This will be done at baseline, 4-5 hours, 3-5 days, 11-13, and 28-35 days after the start of the intervention
Cold immersion pain tolerance	Pain tolerance will be measured by recording the number of seconds the participant is willing to keep their hand immersed in a 5 degree celsius cold bath, up to a maximum of 120 sec.	This will be done at baseline, 3-5 days, 11-13, and 28-35 days after the start of the intervention
Pain wind-up	Pain sensitisation will be measured using a wind-up paradigm (temporal summation) with thermal stimulation (heat simulation). The thermal probe will start at 32 deg C and increase in temperature (100 deg C/s) to 49 deg C. After a duration of 800 ms, the temperature will return to baseline. Participants will be asked for a pain rating on a scale form 0 (not painful) to 10 (extremely painful). Subsequently, a series of 10 heat stimuli (identical to the once above, ISI 400 ms) will be applied. Participants will be asked to rate the most intense pain that they felt across the series, using the same 0-10 rating scale. The difference in pain ratings in response to the series and to the single stimulus will be used as the outcome measure. Higher (positive) ratings will indicate a stronger sensitisation to repeated painful stimuli. In contrast, negative values will indicate habituation to repeated painful stimuli.	This will be done at baseline, 4-5 hours, 3-5 days, 11-13, and 28-35 days after the start of the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive and negative affect	State positive and negative affect will be measured using the The Positive And Negative Affect Schedule Now (PANAS-N) (PANAS-N; adapted from Watson et al., 1988).	This will be done at baseline, 4-5 hours, 3-5 days, 11-13, and 28-35 days after the start of the intervention
State anxiety	State anxiety will be measured using the State-Trait Anxiety Inventory (STAI), which produces a minimum score of 20 and a maximum score of 80, where higher scores indicate greater anxiety.	This will be done at baseline, 4-5 hours, 3-5 days, 11-13, and 28-35 days after the start of the intervention
Sleep quality	Sleep quality will be measured using the Pittsburgh Sleep Quality Index (PSQI), which results in a score ranging between 0 and 21, where higher scores indicate worse sleep quality.	This will be done at baseline, 3-5 days, 11-13, and 28-35 days after the start of the intervention
Dietary intake	Dietary intake will be measured using the Mediterranean Diet Adherence Screener(MEDAS), which produces a score ranging between 0 and 14, where higher scores indicate greater adherence to the Mediterranean diet.	This will be measured at baseline during their first visit only

Collaborators and Investigators

• Sponsor: University of Reading
• Collaborators: INNOPURE

Publications and helpful links

General Publications

• Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. doi: 10.1037//0022-3514.54.6.1063.
• Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.
• Martinez-Gonzalez MA, Garcia-Arellano A, Toledo E, Salas-Salvado J, Buil-Cosiales P, Corella D, Covas MI, Schroder H, Aros F, Gomez-Gracia E, Fiol M, Ruiz-Gutierrez V, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Munoz MA, Warnberg J, Ros E, Estruch R; PREDIMED Study Investigators. A 14-item Mediterranean diet assessment tool and obesity indexes among high-risk subjects: the PREDIMED trial. PLoS One. 2012;7(8):e43134. doi: 10.1371/journal.pone.0043134. Epub 2012 Aug 14.
• Spielberger, C. D., Gonzalez-Reigosa, F., Martinez-Urrutia, A., Natalicio, L. F., & Natalicio, D. S. (1971). The state-trait anxiety inventory. Revista Interamericana de Psicologia/Interamerican journal of psychology, 5(3 & 4).

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: May 10, 2024
• First Submitted That Met QC Criteria: May 10, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2024
• Last Update Submitted That Met QC Criteria: May 21, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Vitamin B6; GABA; Excitation-Inhibition balance
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Vitamin B 6; Pyridoxal; Pyridoxine
• Other Study ID Numbers: UREC24/13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No