The Effects of Vitamin B6 Supplementation on Pain Thresholds and Tolerance

NCT06415383 | Completed Phase 1

• 1 other identifier: UREC24/13
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pain

Keywords

Vitamin B6; GABA; Excitation-Inhibition balance

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (4)

• State 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

• Positive and negative affect

  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

  This will be done at baseline, 3-5 days, 11-13, and 28-35 days after the start of the intervention

• Dietary intake

  This will be measured at baseline during their first visit only

Study Arms (2)

Vitamin-B6

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Vitamin B6 100 MG DRUG

Vitamin B6 in for the form of pyridoxal phosphate (PLP)

Vitamin-B6

Placebo OTHER

Placebo tablet containing microcrystalline cellulose

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• INNOPURE: collaborator
• University of Reading: lead

Study Sites (1)

University of Reading

Reading, Berkshire, RG6 6AL, United Kingdom

Location

Related Publications (4)

• 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).

  BACKGROUND

• 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.

  PMID: 3397865 BACKGROUND

• 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.

  PMID: 2748771 BACKGROUND

• 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.

  PMID: 22905215 BACKGROUND

MeSH Terms

Conditions

Pain

Interventions

Vitamin B 6

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Picolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: May 10, 2024
• First Posted: May 16, 2024
• Study Start: May 30, 2024
• Primary Completion: March 1, 2025
• Study Completion: June 30, 2025
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)