PainPhase 2TAPNCT00351819

Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception

A Phase 2 study testing AndroGel in people with Pain and Hypogonadism, run by Boston University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 100 years, men only
Conditions the study is for: Pain, Hypogonadism
What is being tested?: AndroGel
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 84 participants
Where: 1 siteUnited States
Study dates: Apr 2006to Nov 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 100 years
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

Men
Age 18 years and older
Non-cancer chronic pain
Serum total testosterone level <350 ng/dl
Consumption of at least 20 mg of hydrocodone (or analgesic equivalent of another opioid) for at least 4 weeks
Absence of hospitalization in the past 2 months

Show all 11Show fewer

No acute illness in the past 2 months
No current anabolic therapy (growth hormone, DHEA, etc)
No current use or consumption in the past 2 months of melatonin
Normal prostate exam
Normal PSA level

Who cannot join

Cancer-related chronic pain
Liver enzymes > 3 times upper limit of normal
Serum creatinine > 2 times upper limit of normal
Neurological disease
Active psychiatric illness
Any addictive drug use

Show all 15Show fewer

Alcoholism (>3 drinks/day)
Patients currently receiving melatonin or anabolic agents
Hospitalization in the past 2 months
Acute illness in the past 2 months
Consumption of < 20 mg of hydrocodone (or analgesic equivalent of another opioid)
Severe BPH
PSA > 4.0 ng/ml
Prostate cancer
Breast cancer

Trial locations and contacts

1 site in 1 country.

United States1 site

Brigham and Women's Hospital
Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception in Men With Chronic Pain Syndrome

Naturally occurring opiates (endorphins) decrease testosterone levels by inhibiting the synthesis of gonadotropin releasing hormone (GnRH) and also inhibiting testosterone synthesis by the testes. Similarly, men with addiction to narcotics and those on exogenous opioids for pain control have decreased serum testosterone levels. Indeed, these men complain of decreased libido, erectile dysfunction and impaired quality of life. Animal studies have shown that gonadectomy results in a decrease in pain threshold in rats and repletion of testosterone elevates that threshold. These observations suggest that testosterone may possess analgesic properties. Hence, the investigators hypothesize that hypogonadism developing in men on opioids results in an increased sensitivity to pain and requirement of higher doses of opioids. In this study, the investigators plan to administer testosterone to men with opioid-induced hypogonadism and evaluate their pain perception, pain sensitivity in response to noxious stimuli and changes in the requirement of opioids in response to testosterone administration.

Hypothesis:

Testosterone replacement in men with opioid-induced hypogonadism will improve pain tolerance, pain perception and quality of life.

Specific aims:

To evaluate the effects of testosterone replacement on pain sensitivity, pain tolerance, and pain modulation in men with opioid-induced hypogonadism.
To determine the effects of testosterone replacement on health-related quality of life.
To determine whether testosterone replacement in hypogonadal men induces changes in the dosage requirements of opioid medications for pain control.

To accomplish our specific aims, the investigators propose a randomized, double blind, placebo-controlled, parallel arm study in which hypogonadal men with non-cancer chronic back pain syndrome on chronic opioids and low testosterone levels (<300 ng/dl) will be randomized to exogenous testosterone replacement therapy vs placebo. Our primary outcome is change in pain tolerance using various external painful stimuli. Secondary outcomes are change in pain sensitivity and modulation, quality of life and opioid requirements.

Conditions: Pain, Hypogonadism
Being tested: AndroGel, Placebo
Keywords: Testosterone, Pain, Opioid, Hypogonadism
Medical subject headings: Pain, Hypogonadism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AndroGelDrug
Also called testosterone gel
5g gel, applied once daily to the upper arms, upper back or shoulders.
PlaceboOther
5g gel, applied once daily to the upper arms, upper back or shoulders.

Study groups in NCT00351819
Study group	Role	What they receive
Androgel (testosterone gel)	Active comparator	Testosterone replacement therapy Receives: Drug: AndroGel
Placebo	Placebo comparator	Placebo gel Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Brief Pain Inventory (BPI) at Week 14
BPI is a self-administered questionnaire that measuring chronic pain. BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score assesses the severity of pain on a continuous scale from 0 (no pain) to 10 (severe pain). The pain interference score corresponds to the item on pain interference, ranging from 0 (does not interfere) to 10(completely interferes). The total score is the sum of the pain severity score and pain interference score, ranging from 0(no pain) to 20 (severe and completely interfered pain).
Measured: Week14 after intervention
Algometer-induced Pressure Pain at Week 14
A digital pressure algometer at the trapezius muscle and the metacarpophalangeal joint of the thumb was used to measure pressure pain thresholds. Higher values represent a better tolerance of pressure pain.
Measured: Week 14 after intervention
Weighted Pinprick Stimulator-induced Mechanical Pain at Week 14
Weighted pinprick stimulators are used to assess mechanical pain. Lower values represent better tolerance of pain.
Measured: Week 14 after intervention
Ice Water-induced Cold Pain and Its After-sensation at Week 14
Cold-pressor tests measure cold-induced pain and its sensation. Time was measured when a participant reached pain tolerance in cold water and after sensation. Higher values of time in Cold pain tolerance and lower values of time in Cold pain after-sensation (30 seconds) represent better tolerance of pain.
Measured: Week 14 after intervention

Secondary outcomes (3)

Sexual Functioning as Assessed by International Index of Erectile Function (IIEF) at Week 14
IIEF is a validated, 15-item questionnaire that assesses 5 domains of sexual function: erectile function (range 1-30), orgasmic function (range 0-10), sexual desire (range 2-10), intercourse satisfaction (range 0-15), and overall sexual satisfaction (range 2-10). Each question was answered on a 6-point or 5-point scale from 0/1 to 5 (best) with a total possible score (sum of 5 domains) range of 5 to 75 with higher scores representing better function.
Measured: Week14 after intervention
Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36) at Week 14
The SF-36 measures 8 domains of the QoL: physical function, bodily pain, vitality, role limitations due to physical problems, general health perceptions, emotional well-being, social function, and role limitations due to emotional problems. Each domain is scored separately from 0 to 100 with higher scores representing better health-related QoL.
Measured: Week 14 after intervention
Pain Catastrophizing Scale (PCS) at Week 14
PCS questionnaire measures self-assessment of pain catastrophizing. This questionnaire consists of 13 items on past painful experiences and rate on 5-point scales ranging from 0 (not at all) to 4 (all the time). The PCS yields three subscale scores assessing rumination (range 0-16), magnification (range 0-12), helplessness (range 0-24), and a composite score (sum of three domains, ranging 0-52). Higher score represents worse painful experiences.
Measured: Values at week 14 after intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2006Nov 2012

First posted13 Jul 2006 (estimated)
Study startApr 2006
Primary completionNov 2012
Study completionNov 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for PainStudies of the same condition, open and under way.
More trials run by Boston UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 84 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00351819
Sponsor's protocol ID: H-27995
Acronym: TAP
Status last verified: May 2017
First submitted: 12 Jul 2006
Last updated: 28 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Bhasin S, Travison TG, O'Brien L, MacKrell J, Krishnan V, Ouyang H, Pencina K, Basaria S. Contributors to the substantial variation in on-treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials. Andrology. 2018 Jan;6(1):151-157. doi: 10.1111/andr.12428. Epub 2017 Oct 5.
PubMed 28981994
Gagliano-Juca T, Icli TB, Pencina KM, Li Z, Tapper J, Huang G, Travison TG, Tsitouras P, Harman SM, Storer TW, Bhasin S, Basaria S. Effects of Testosterone Replacement on Electrocardiographic Parameters in Men: Findings From Two Randomized Trials. J Clin Endocrinol Metab. 2017 May 1;102(5):1478-1485. doi: 10.1210/jc.2016-3669.
PubMed 27992261
Basaria S, Travison TG, Alford D, Knapp PE, Teeter K, Cahalan C, Eder R, Lakshman K, Bachman E, Mensing G, Martel MO, Le D, Stroh H, Bhasin S, Wasan AD, Edwards RR. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial. Pain. 2015 Feb;156(2):280-288. doi: 10.1097/01.j.pain.0000460308.86819.aa.
PubMed 25599449

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 28 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception in Men With Chronic Pain Syndrome
ClinicalTrials.gov ID: NCT00351819
Acronym / sponsor ID: TAP / H-27995
Conditions: Pain, Hypogonadism
Keywords: Testosterone, Pain, Opioid, Hypogonadism
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 84 participants (actual)
Lead sponsor: Boston UniversityUniversity, hospital or other
Study start: Apr 2006
Primary completion: Nov 2012 (actual)
Study completion: Nov 2012 (actual)
First posted: 13 Jul 2006 (estimated)
Results: Posted 28 Jun 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Hypothesis:

Testosterone replacement in men with opioid-induced hypogonadism will improve pain tolerance, pain perception and quality of life.

Specific aims:

To evaluate the effects of testosterone replacement on pain sensitivity, pain tolerance, and pain modulation in men with opioid-induced hypogonadism.
To determine the effects of testosterone replacement on health-related quality of life.
To determine whether testosterone replacement in hypogonadal men induces changes in the dosage requirements of opioid medications for pain control.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Androgel (testosterone gel)	Active comparator	Drug: AndroGelTestosterone replacement therapy
Placebo	Placebo comparator	Other: PlaceboPlacebo gel

Who may qualify

Ages: 18 to 100 years
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Men
Age 18 years and older
Non-cancer chronic pain
Serum total testosterone level <350 ng/dl
Consumption of at least 20 mg of hydrocodone (or analgesic equivalent of another opioid) for at least 4 weeks

Key exclusion criteria (15 listed)

Cancer-related chronic pain
Liver enzymes > 3 times upper limit of normal
Serum creatinine > 2 times upper limit of normal
Neurological disease
Active psychiatric illness

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AndroGelAlso: testosterone gel5g gel, applied once daily to the upper arms, upper back or shoulders.	Drug	Androgel (testosterone gel)
Placebo5g gel, applied once daily to the upper arms, upper back or shoulders.	Other	Placebo

Primary outcome

Brief Pain Inventory (BPI) at Week 14
Time frame: Week14 after intervention
BPI is a self-administered questionnaire that measuring chronic pain. BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score assesses the severity of pain on a continuous scale from 0 (no pain) to 10 (severe pain). The pain interference score corresponds to the item on pain interference, ranging from 0 (does not interfere) to 10(completely interferes). The total score is the sum of the pain severity score and pain interference score, ranging from 0(no pain) to 20 (severe and completely interfered pain).
Algometer-induced Pressure Pain at Week 14
Time frame: Week 14 after intervention
A digital pressure algometer at the trapezius muscle and the metacarpophalangeal joint of the thumb was used to measure pressure pain thresholds. Higher values represent a better tolerance of pressure pain.
Weighted Pinprick Stimulator-induced Mechanical Pain at Week 14
Time frame: Week 14 after intervention
Weighted pinprick stimulators are used to assess mechanical pain. Lower values represent better tolerance of pain.
Ice Water-induced Cold Pain and Its After-sensation at Week 14
Time frame: Week 14 after intervention
Cold-pressor tests measure cold-induced pain and its sensation. Time was measured when a participant reached pain tolerance in cold water and after sensation. Higher values of time in Cold pain tolerance and lower values of time in Cold pain after-sensation (30 seconds) represent better tolerance of pain.

3 secondary outcomes

Sexual Functioning as Assessed by International Index of Erectile Function (IIEF) at Week 14
Time frame: Week14 after intervention
Health Quality of Life (QoL) as Assessed by Short Form 36 (SF-36) at Week 14
Time frame: Week 14 after intervention
Pain Catastrophizing Scale (PCS) at Week 14
Time frame: Values at week 14 after intervention

Results and safety

Results posted to the registry on 28 Jun 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Androgel (Testosterone Gel)	43	36
Placebo	41	29

Primary outcome: Brief Pain Inventory (BPI) at Week 14

Time frame: Week14 after intervention. Mean (Standard Deviation). Unit: units on a scale

Measure	Androgel (Testosterone Gel) n = 36	Placebo n = 29
Total score	10.2 (3.8)	9.7 (3.3)
Severity	5.3 (1.7)	5.1 (1.6)
Interference	5.0 (2.3)	4.7 (1.9)

Population analysed: All available data expressed as absolute values at week 14.

Primary outcome: Algometer-induced Pressure Pain at Week 14

Time frame: Week 14 after intervention. Mean (Standard Deviation). Unit: kPa/cm2

Measure	Androgel (Testosterone Gel) n = 36	Placebo n = 29
Trapezius	379.4 (194.7)	315.9 (151.6)
Thumb	409.7 (167.9)	326.4 (187.3)

Primary outcome: Weighted Pinprick Stimulator-induced Mechanical Pain at Week 14

Time frame: Week 14 after intervention. Mean (Standard Deviation). Unit: watts

Measure	Androgel (Testosterone Gel) n = 36	Placebo n = 29
First Stimulus	10.9 (8.4)	11.7 (13.2)
10th Stimulus	21.9 (17.4)	22.2 (23.5)

Primary outcome: Ice Water-induced Cold Pain and Its After-sensation at Week 14

Time frame: Week 14 after intervention. Mean (Standard Deviation). Unit: seconds

Measure	Androgel (Testosterone Gel) n = 36	Placebo n = 29
Cold pain tolenrance	54.2 (55.9)	54.1 (50.9)
Cold pain after sensation: 30s	13.1 (18.4)	13.9 (15.1)

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Androgel (Testosterone Gel)	1 of 43 (2.3%)	6 of 43 (14%)	Not reported
Placebo	2 of 41 (4.9%)	5 of 41 (12.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28981994Bhasin S, Travison TG, O'Brien L, MacKrell J, Krishnan V, Ouyang H, Pencina K, Basaria S. Contributors to the substantial variation in on-treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials. Andrology. 2018 Jan;6(1):151-157. doi: 10.1111/andr.12428. Epub 2017 Oct 5.
Derived from this study: PubMed 27992261Gagliano-Juca T, Icli TB, Pencina KM, Li Z, Tapper J, Huang G, Travison TG, Tsitouras P, Harman SM, Storer TW, Bhasin S, Basaria S. Effects of Testosterone Replacement on Electrocardiographic Parameters in Men: Findings From Two Randomized Trials. J Clin Endocrinol Metab. 2017 May 1;102(5):1478-1485. doi: 10.1210/jc.2016-3669.
Derived from this study: PubMed 25599449Basaria S, Travison TG, Alford D, Knapp PE, Teeter K, Cahalan C, Eder R, Lakshman K, Bachman E, Mensing G, Martel MO, Le D, Stroh H, Bhasin S, Wasan AD, Edwards RR. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial. Pain. 2015 Feb;156(2):280-288. doi: 10.1097/01.j.pain.0000460308.86819.aa.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Shehzad Basaria, MD principal investigator

Brigham and Women's Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AndroGel in people with Pain and Hypogonadism, run by Boston University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brief Pain Inventory (BPI) at Week 14 (time frame: Week14 after intervention). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00351819, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2017.