Mechanistic Evaluation of Polypharmacy Effects for Pain

NCT07846020 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: HP-00118502R01DA061796
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-group, within-subject, double-blind, double-dummy, placebo-controlled study evaluating whether gabapentin (Neurontin) changes the analgesic, safety, and subjective effects of the opioid hydromorphone (Dilaudid) when the two are combined.

Conditions

Chronic Lower Back Pain (CLBP)

Outcome Measures

Primary Outcomes (7)

• Peak change from baseline Drug Effect

  Peak self-reported "Drug Effect" on a visual analogue scale (0-100) minus baseline ratings of self-reported "Drug Effect" on a visual anaogue scale (0-100)

  8 hour study sessions

• Peak change from baseline Good Effect

  Peak self-reported "Good Effect" on a visual analogue scale (0-100) minus baseline ratings of self-reported "Good Effect" on a visual anaogue scale (0-100), where lower scores indicate no effect and greater scores indicate maximum effect.

  Baseline (0.5 hours before drug administration) and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 8 hours after drug administration

• Peak Cold Pressor Test Tolerance change from baseline score

  Peak Cold Pressor Test Tolerance Score minus baseline Peak Cold Pressor Test Tolerance score. Outcome ranges from 0-60 seconds, 0 indicating low analgesic effect and 60 indicating high analgesic effects.

  Baseline (0.5 hours before drug administration) and 4 and 6 hours after study drug administration

• Peak Cold Pressor Test Threshold change from baseline score

  Peak Cold Pressor Test Threshold Score minus baseline Peak Cold Pressor Test Threshold score. Outcome ranges from 0-60 seconds, 0 indicating low analgesic effect and 60 indicating high analgesic effects.

  Baseline (0.5 hours before drug administration) and 4 and 6 hours after study drug administration

• Peak Heat Pain with Capsaicin Threshold change from baseline score

  Peak Heat Pain with Capsaicin Threshold score minus baseline Peak Heat Pain with Capsaicin Threshold score. Outcome ranges from 0-100, 0 indicating no pain and 100 indicating extreme pain.

  Baseline (0.5 hours before drug administration) and 4 and 6 hours after study drug administration

• Peak Heat Pain with Capsaicin Tolerance Change from Baseline Score

  Peak Heat Pain with Capsaicin Tolerance score minus baseline Peak Heat Pain with Capsaicin Tolerance score. Outcome ranges from 0-100, 0 indicating no pain and 100 indicating extreme pain.

  Baseline (0.5 hours before drug administration) and 4 and 6 hours after study drug administration

• Peak change from baseline Bad Effect

  Peak self-reported "Bad Effect" on a visual analogue scale (0-100) minus baseline ratings of self-reported "Bad Effect" on a visual anaogue scale (0-100) where lower scores indicate no effect and greater scores indicate maximum effect.

  Baseline (0.5 hours before drug administration) and 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 8 hours after drug administration

Study Arms (6)

Placebo hydromorphone, Placebo gabapentin

PLACEBO COMPARATOR

0mg oral hydromorphone, 0mg oral gabapentin

Drug: Within-subject test of blinded study medications (Placebo, Hydromorphone, Gabapentin)

Active hydromorphone, Low dose gabapentin

EXPERIMENTAL

4mg oral hydromorphone, 300mg oral gabapentin

Drug: Within-subject test of blinded study medications (Placebo, Hydromorphone, Gabapentin)

Active hydromorphone, High dose gabapentin

EXPERIMENTAL

4mg oral hydromorphone, 900mg oral gabapentin

Drug: Within-subject test of blinded study medications (Placebo, Hydromorphone, Gabapentin)

Placebo hydromorphone, Low dose gabapentin

ACTIVE COMPARATOR

0mg oral hydromorphone, 300mg oral gabapentin

Drug: Within-subject test of blinded study medications (Placebo, Hydromorphone, Gabapentin)

Placebo hydromorphone, High dose gabapentin

ACTIVE COMPARATOR

0mg oral hydromorphone, 900mg oral gabapentin

Drug: Within-subject test of blinded study medications (Placebo, Hydromorphone, Gabapentin)

Active hydromorphone, placebo gabapentin

ACTIVE COMPARATOR

4mg oral hydromorphone, 0mg gabapentin

Drug: Within-subject test of blinded study medications (Placebo, Hydromorphone, Gabapentin)

Interventions

Within-subject test of blinded study medications (Placebo, Hydromorphone, Gabapentin) DRUG

Within-subject double-blind, double-dummy, study design wherein all participants received all drug combinations (Placebo + Placebo, Hydromorphone + Placebo, Low Dose Gabapentin + Placebo, High Dose Gabapentin + Placebo, Low Dose Gabapentin + Hydromorphone, High Dose Gabapentin + Hydromorphone) in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.

Active hydromorphone, High dose gabapentin; Active hydromorphone, Low dose gabapentin; Active hydromorphone, placebo gabapentin; Placebo hydromorphone, High dose gabapentin; Placebo hydromorphone, Low dose gabapentin; Placebo hydromorphone, Placebo gabapentin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• Lifetime history of opioid use
• Medically cleared to take study medications
• Chronic Lower Back Pain
• Agree to use effective form of contraception throughout enrollment

You may not qualify if:

• Pregnant or breastfeeding
• Have evidence of physical dependence on or current use of any central nervous system depressants including but not limited to alcohol, benzodiazepines, opioids, gabapentinoids, or barbiturates
• Past 30-day use of certain pain medications
• Evidence of past 7-day nonmedical drug use
• Known hypersensitvity, allergy to, or history of adverse reactions to study medications
• Are currently taking a medication or have a condition that is contraindicated with either study medication
• Have evidence of current or past significant medical/psychiatric illness
• Have a history of clinically significant cardiac arrhythmias or vasospastic disease
• Have evidence of renal or hepatic impairment
• Current suicidal ideation or behavior, or a history of a suicide attempt within the past 2 years
• Have any condition that may increases the risk for respiratory depression

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Kahlert Institute for Addiction Medicine

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Interventions

Hydromorphone; Gabapentin

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Amines; Organic Chemicals; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

Sarah Dowell

CONTACT

667-351-5088; sdowell@som.umaryland.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Drug class is blinded to participant.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Within-subject test of blinded study medications

Study Record Dates

• First Submitted: September 14, 2026
• First Posted: September 29, 2026
• Study Start (Estimated): January 15, 2027
• Primary Completion (Estimated): January 15, 2032
• Study Completion (Estimated): April 1, 2032
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)